Non-tuberculous mycobacteria (NTM) infections are increasingly recognized as a public health concern, yet their distribution and antibiotic resistance patterns on Hainan Island, China's tropical hotspot, remain understudied. This study analyzes 158 clinical respiratory samples from 2015 to 2018 across 14 cities, identifying 118 NTM isolates from 24 species. Predominant species include Mycobacterium abscessus (23.73%), M. intracellulare (22.03%), and M. simiae (14.41%). Spatial mapping reveals elevated prevalence in coastal areas, with no significant north-south divergence on the island (Bray-Curtis dissimilarity: 0.5954, P = 0.694), but substantial differences from mainland China (North: 0.9604, P = 0.0011; South: 0.9340, P = 0.0013). Antimicrobial testing of M. abscessus isolates indicates complete resistance to doxycycline (100%), moderate sensitivity to amikacin (71.4%) and linezolid (50.0%), and variable responses to other agents. Novel detections of M. algericus and M. sinensis expand Hainan's NTM diversity. These findings establish a baseline for region-specific surveillance, antibiotic stewardship, and intervention strategies to combat NTM misdiagnosis and mortality in tropical settings.IMPORTANCEPrevious studies have not covered the distribution of non-tuberculous mycobacteria (NTM) in various regions of Hainan Province. This study provides the first comprehensive geographic map of NTM in Hainan, China's tropical island hotspot. By monitoring NTM across 14 cities over 4 years, we reveal key patterns in their habitat preferences and dominant species in infections. These findings establish a foundational framework for region-specific surveillance and treatment protocols in Hainan and offer a replicable model for global tropical regions combating NTM infections. Ultimately, this work empowers public health initiatives to reduce misdiagnosis, enhance antibiotic stewardship, and lower mortality rates among at-risk populations.

Background Non-tuberculous mycobacteria (NTM) represent a diverse group of environmental mycobacteria, with certain species implicated in infections affecting multiple tissues, including the lungs. The incidence of NTM-related diseases has been on the rise globally, particularly in developing countries. This study aimed to systematically investigate the ecological distribution, molecular identification, and antibiotic susceptibility profiles of NTM isolates in Hainan Island, furnishing a scientific basis for local control and prevention strategies. Methods From 2015 to 2018, 158 suspected NTM samples were collected across 14 cities on Hainan Island. Following standardized sample processing and DNA extraction, molecular identification was conducted through PCR amplification of the rpoB and hsp65 genes, and sequencing, with species confirmation via GenBank database comparison. Phylogenetic analysis was performed to elucidate interspecies relationships and drug susceptibility testing was carried out for five antibiotics on M. abscessus isolates. Results 118 NTM isolates were successfully identified, encompassing 24 distinct species. M. abscessus and M. intracellulare, accounting for 23.73% and 22.03% respectively, were the most prevalent. Phylogenetic analysis revealed clusters indicative of pathogenic and potentially pathogenic traits among different NTM species, with M. abscessus and M. fortuitum clustering as rapidly growing, pathogenic mycobacteria. Drug sensitivity testing indicated universal resistance of M. abscessus to doxycycline, yet high sensitivity to amikacin (71.4%) and linezolid (50.0%). Additionally, non-NTM species such as Nocardia thailandica, and Tsukamurella paurometabola were detected, suggesting potential misdiagnosis in clinical settings. Conclusion This study provides a comprehensive dataset on the ecological distribution, molecular characterization, and antibiotic resistance of NTM in Hainan Island, highlighting the dominance of M. abscessus and M. intracellulare in local NTM infections. ### Competing Interest Statement The authors have declared no competing interest.

Growing evidence describes the host immune response mechanism involved in malaria. Despite the spread of drug resistance, chloroquine (CQ) remains the main antimalarial drug in most countries in Latin America and Asia. Studies have indicated an immunomodulatory activity of CQ, however, the potential implications for CQ on immunological memory recognizing the malaria parasite are still being elucidated. Our study suggests that CQ treatment significantly delayed the initiation of parasitemia during infection of mice with the rodent malaria parasite, Plasmodium chabaudi (P.c.). Additionally, there was a decrease in T follicular helper cells (Tfh), CD4+ effector memory T cells, memory B cells (MBC), IgG2a memory B cells, along with IgG2a plasma cells; while antibody production was not affected at the observation time points. After PD-1 blockade and CQ treatment, no reductions in the numbers of CD4+ effector memory T cells, MBC, and IgG2a memory B cells were observed compared with the P.c. group. Therefore, CQ might regulate immunological memory via the PD-1/PD-L1 signaling pathway. Compared with antibody secretion, the inhibition of CQ on immune memory cells was a more sensitive indicator.

目的 探讨γδT细胞在感染致死型约氏疟原虫(P.y 17XL)的BALB/c小鼠免疫应答中作用及机制.方法 6～8周雌性BALB/c小鼠随机分为对照组、P.y 17XL感染组和γδT消除组.小鼠经腹腔注射P.y 17XL感染红细胞1 × 106个/只.γδT消除方法为感染前连续2d腹腔注射TCR γ/δ单抗(150 μg只),对照组和P.y 17XL感染组注射等体积同型对照抗体.动态检测红细胞感染率并观察小鼠生存率.感染后3、5d,制备脾细胞悬液,流式细胞术检测γδT、DCs和Th1细胞数量;体外培养脾细胞,48h后收集上清,ELISA检测γ干扰素(IFN-γ)和肿瘤坏死因子α(TNF-α)水平.结果 与对照组比较,感染后3、5d,P.y 17XL感染组小鼠脾脏中γδT细胞数量明显升高(P＜0.05),消除组小鼠脾脏中γδT细胞数量明显降低(P＜0.01).感染后5d,与感染组比较,γδT消除组小鼠脾脏中DC细胞数量及活化水平明显增加,IFN-γ和TNF-α含量明显升高,Th1细胞数量明显增加.结论 γδT细胞参与P.y 17XL红内期急性期感染;消除γδT细胞后,Th1型免疫应答代偿性增加.

Bacillus Calmette-Guérin (BCG) is an attenuated Mycobacterium tuberculosis vaccine.We performed a series of co-infection experiments with BCG-Plasmodium chabaudi chabaudi Landau, 1965 AS using C57BL/6 mice to analyse whether BCG can affect the development of protective immunity to infection with Plasmodium spp.and the mechanism of this protection.We divided mice into four groups: BCG-inoculation 4 weeks prior to P. c. chabaudi AS infection (B-4w-Pc); simultaneous BCG-inoculation and P. c. chabaudi AS infection (Pc+B); BCG-inoculation 3 days post P. c. chabaudi AS (Pc-3-B) infection; and mono-P.c. chabaudi AS infection as control (Pc).The parasitemia level in the B-4w-Pc group was noticeably higher than control group at 6-19 days post infection (dpi).Compared with the control group, the proportion of CD4 + CD69 + T cells was significantly reduced 5, 8 and 12 dpi, but the proportion of CD4 + CD25 + Foxp3 + Tregs was significantly increased in the B-4w-Pc group on 5 and 8 dpi.The B-4w-Pc group also demonstrated reduced levels of IFN-γ and TNF-α on 5 and 8 dpi and significantly elevated level of IL-10 on 12 dpi.There were significantly fewer mDCs (CD11c + CD11b + ) and pDCs (CD11c + B220 + ) in the B-4w-Pc group than the control group at all the time points post infection and the expression of MHC II was noticeably reduced on day 8 pi.Our findings confirmed that BCG inoculation prior to Plasmodium infection resulted in excessive activation and proliferation of Tregs and upregulation of anti-inflammatory mediators, which inhibited establishment of a Th1-dominant immune response during the early stages of Plasmodium infection by inhibiting dendritive cells response.BCG inoculation prior to P. c. chabaudi AS infection may contribute to overgrowth of parasites as well as mortality in mice.

To investigate the genetic diversity of the Plasmodium falciparum apical membrane antigen 1 (PfAMA1) gene in Southeast Asia, we determined PfAMA1 sequences from 135 field isolates collected from the China–Myanmar border area and compared them with 956 publically available PfAMA1 sequences from seven global P. falciparum populations. This analysis revealed high genetic diversity of PfAMA1 in global P. falciparum populations with a total of 229 haplotypes identified. The genetic diversity of PfAMA1 gene from the China–Myanmar border is not evenly distributed in the different domains of this gene. Sequence diversity in PfAMA1 from the China–Myanmar border is lower than that observed in Thai, African and Oceanian populations, but higher than that in the South American population. This appeared to correlate well with the levels of endemicity of different malaria-endemic regions, where hyperendemic regions favor genetic cross of the parasite isolates and generation of higher genetic diversity. Neutrality tests show significant departure from neutrality in the entire ectodomain and Domain I of PfAMA1 in the China–Myanmar border parasite population. We found evidence supporting a substantial continent-wise genetic structure among P. falciparum populations, with the highest genetic differentiation detected between the China–Myanmar border and the South American populations. Whereas no alleles were unique to a specific region, there were considerable geographical differences in major alleles and their frequencies, highlighting further necessity to include more PfAMA1 alleles in vaccine designs.

BACKGROUND:With the premise of diminishing parasite genetic diversity following the reduction of malaria incidence, the analysis of polymorphic antigenic markers may provide important information about the impact of malaria control on local parasite populations. Here we evaluated the genetic diversity of Plasmodium vivax apical membrane antigen 1 (Pvama1) gene in a parasite population from the China-Myanmar border and compared it with global P. vivax populations.METHODS:We performed evolutionary analysis to examine the genetic diversity, natural selection, and population differentiation of 73 Pvama1 sequences acquired from the China-Myanmar border as well as 615 publically available Pvama1 sequences from seven global P. vivax populations.RESULTS:A total of 308 Pvama1 haplotypes were identified among the global P. vivax isolates. The overall nucleotide diversity of Pvama1 gene among the 73 China-Myanmar border parasite isolates was 0.008 with 41 haplotypes being identified (Hd = 0.958). Domain I (DI) harbored the majority (26/33) of the polymorphic sites. The McDonald Kreitman test showed a significant positive selection across the ectodomain and the DI of Pvama1. The fixation index (F ST ) estimation between the China-Myanmar border, Thailand (0.01) and Myanmar (0.10) showed only slight geographical genetic differentiation. Notably, the Sal-I haplotype was not detected in any of the analyzed global isolates, whereas the Belem strain was restricted to the Thai population. The detected mutations are mapped outside the overlapped region of the predicted B-cell epitopes and intrinsically unstructured/disordered regions.CONCLUSIONS:This study revealed high levels of genetic diversity of Pvama1 in the P. vivax parasite population from the China-Myanmar border with DI displaying stronger diversifying selection than other domains. There were low levels of population subdivision among parasite populations from the Greater Mekong Subregion.

通过外源性给予LPS,探讨TLR4在疟疾感染早期免疫应答的作用特点及其免疫调节作用.通过Plasmodium yoelii 17XL感染的BALB/c小鼠建立鼠疟模型并在感染前给予LPS,于感染第0、3和5天制备脾细胞悬液,通过流式细胞术检测脾细胞悬液中TLR4+ DCs和Tregs百分含量;ELISA方法检测脾细胞培养上清中IFN-γ和IL-10水平.结果显示,LPS处理能够显著延长宿主生存期,降低原虫血症水平,同时显著提升脾上清中的IFN-γ水平,降低抑炎性细胞因子IL-10水平.在感染早期,LPS处理可诱导Th1型免疫应答的有效建立,明显遏制P.y 17XL红内期疟原虫的感染进程.

Phenylhydrazine (PHZ) treatment is generally used to enhance parasitemia in infected mice models. Transient reticulocytosis is commonly observed in iron-deficient anemic hosts after treatment with iron supplementation, and is also associated with short-term hemolysis caused by PHZ treatment. In this study, we investigated the relationship between reticulocytosis and cerebral malaria (CM) in a murine model induced by PHZ administration before Plasmodium berghei ANKA (PbA) infection. Mortality and parasitemia were checked daily. Pro-inflammatory cytokines and IL-10 were quantified by ELISA. The expression of CXCL9, CXCL10, CCL5, and CXCR3 mRNAs was determined by real-time PCR. Brain sequestration of CD4(+) and CD8(+) T cells and populations of splenic Th1 CD4(+) T cells, dendritic cells (DCs), CD11b(+) Gr1(+) cells, and regulatory T cells (Tregs) were assessed by FACS. PHZ administration dramatically increased parasitemia from day 3 to day 5 post infection (p.i.) compared with the untreated control infected mice group; also, CM developed at day 5 p.i., compared with day 7 p.i. in untreated control infected mice, as well as significantly decreased blood-brain barrier function (P < 0.001). PHZ administration during PbA infection significantly increased the expression of CXCL9 (P <0.05) and VCAM-1 (P <0.001) in the brain, increased the expression of CXCL10, CCL5 and CXCR3, and significantly increased the recruitment of CD4(+) and CD8(+) T cells (P <0.001 and P <0.01, respectively) as well as CD11b(+) Gr1(+) cells to the brain. In addition, PHZ administration significantly increased the numbers of IL-12-secreting DCs at days 3 and 5 p.i. compared to those of untreated control infected mice (P <0.001 and P <0.01, respectively). Consequently, the activation of CD4(+) T cells, especially the expansion of the Th1 subset (P <0.05), was significantly and dramatically enhanced and was accompanied by marked increases in the production of protein and/or mRNA of the Th1-type pro-inflammatory mediators, IFN-γ and TNF-α (P <0.01 for both for protein; P <0.05 for TNF-α mRNA). Our results suggest that, compared to healthy individuals, people suffering from reticulocytosis may be more susceptible to severe malaria infection in malaria endemic areas. This has implications for the most appropriate selection of treatment, which may also cause reticulocytosis in patients living in such areas.

ABSTRACT Cerebral malaria (CM) is associated with excessive host proinflammatory responses and endothelial activation. The hematopoietic hormone erythropoietin (EPO) possesses neuroprotective functions in animal models of ischemic-hypoxic, traumatic, and inflammatory injuries. In the Plasmodium berghei ANKA model of experimental CM (ECM), recombinant human EPO (rhEPO) has shown evident protection against ECM. To elucidate the mechanism of EPO in this ECM model, we investigated the effect of rhEPO on host cellular immune responses. We demonstrated that improved survival of mice with ECM after rhEPO treatment was associated with reduced endothelial activation and improved integrity of the blood-brain barrier. Our results revealed that rhEPO downregulated the inflammatory responses by directly inhibiting the levels and functions of splenic dendritic cells. Conversely, rhEPO treatment led to significant expansion of regulatory T cells and increased expression of the receptor cytotoxic T lymphocyte antigen 4 (CTLA-4). The data presented here provide evidence of the direct effect of rhEPO on host cellular immunity during ECM.

Different functions have been attributed to CD4(+)CD25(+)Foxp3(+) regulatory T-cells (Tregs) during malaria infection. Herein, we describe the disparity in Treg response and pro- and anti-inflammatory cytokines during infection with Plasmodium berghei ANKA between young (3-week-old) and middle-aged (8-month-old) C57BL/6 mice. Young mice were susceptible to cerebral malaria (CM), while the middle-aged mice were resistant to CM and succumbed to hyperparasitemia and severe anemia. The levels of pro-inflammatory cytokines, such as TNF-α, in young CM-susceptible mice were markedly higher than in middle-aged CM-resistant mice. An increased absolute number of Tregs 3-5 days post-inoculation, co-occurring with elevated IL-10 levels, was observed in middle-aged CM-resistant mice but not in young CM-susceptible mice. Our findings suggest that Treg proliferation might be associated with the suppression of excessive pro-inflammatory Th1 response during early malaria infection, leading to resistance to CM in the middle-aged mice, possibly in an IL-10-dependent manner.

Although great efforts have been undertaken for the development of malaria vaccines, no completely effective malaria vaccines are available yet. Despite being clinically silent, the pre-erythrocytic stage is considered an ideal target for the development of malaria vaccines. Sporozoite asparagine-rich protein 1 (SAP1) is a sporozoite-localized protein that regulates the expression of UIS (upregulated in infectious sporozoites) genes, which are essential for the infectivity of sporozoites. In this study, a recombinant DNA vaccine encoding a predicted antigenic determinant region of Plasmodium yoelii SAP1 (PySAP1) was constructed. Immunization of mice with this DNA vaccine construct resulted in significant elevation of cytokines such as IFN-γ, IL-2, IL-4 and IL-10, and total IgG as compared with control groups immunized with either the empty DNA vector or saline. After challenge with sporozoites, the group receiving the DNA vaccine showed delayed development of parasitemia and prolonged survival time compared with the control group. The DNA vaccine provided partial protection against P. yoelii 17XL infection, with an overall protection rate of 20%. In addition, the DNA vaccine did not show integration into the host genome. Further studies of SAP1 are needed to test whether it can be used as subunit vaccine candidate.

为研究预感染旋毛形线虫后BALB/c小鼠抵御夏氏疟原虫攻击感染的能力,实验组（TPC）分别在小鼠感染旋毛形线虫1 w（TPC1）和3 w（TPC3）后感染夏氏疟原虫,对照组（PC）单独感染夏氏疟原虫,观察小鼠原虫血症及体重的变化,并采用Real-Time RCR扩增法分析转录因子T-bet和Gata-3表达水平的消长。与PC组相比,TPC1组原虫血症峰值降低,T-bet表达水平升高,Gata-3表达水平降低;TPC3组原虫血症出现时间推迟,峰值升高,T-bet表达水平降低,Gata-3表达水平升高;TPC组体重均下降,TPC组与PC组均于感染后25 d左右自愈。旋毛虫预感染使小鼠对疟原虫的抗感染能力增强,但混合感染并不影响宿主最终清除疟原虫的能力。

Event Abstract Back to Event Casein diets prevent experimental cerebral malaria by enhancing host pro-inflammatory immune responses during early stage Yonghui Feng1, Xiaodan Sun1, Xu Wei1, Jun Liu1 and Yaming Cao1* 1 China Medical University, China Cerebral malaria (CM) is still a severe complication threating to the children under five in malaria endemic areas. Malaria infection reduces the nutritional status of children, and malnutrition aggravates the mortality of malaria. Casein hydrolyzate can regulate host immune responses. Here, we investigate the related immune mechanisms in casein diet preventing experimental cerebral malaria (ECM). C57BL/6 mice were fed 0% (NC group), 5%, 20% and 35% casein diet for one month before infection with Pb ANKA, respectively. Casein diets can reduce the parasitemia and prolong survival of ECM mice. On d3 p.i., casein diets increased splenic Th1 cells and macrophages (P<0.05), and the similar trend was observed in IFN-γ, TNF-α and NO levels (P<0.05). However, on d5 p.i., Th1 cells and macrophages and related IFN-γ, TNF-α and NO levels were significantly lower than NC group (P <0.05), and CD4+, CD8+ T cells, neutrophils and IFN-γ, TNF-α, ICAM-1, VCAM-1 mRNA levels in the brain, and ICAM-1 and VCAM-1 expression levels in the brain vascular endotheliocyte were significantly down-regulated in casein diets groups (compared with NC group, P <0.05). Casein diet does not affect the number of Treg and IL-10 levels. These data present the mechanism of casein diets in preventig ECM by improving host pro-inflammatory immune responses to control parasitemia during the early stage of infection, thereby reducing inappropriate pro-inflammatory immune responses to maintain blood–brain barrier integrity, which offered a importantly new theoretical basis for the prevention of children CM. Keywords: experimental cerebral malaria, Caseins, pro-inflammatory immune response, Macrophages, Adhesion molecules Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Host-pathogen interactions Citation: Feng Y, Sun X, Wei X, Liu J and Cao Y (2013). Casein diets prevent experimental cerebral malaria by enhancing host pro-inflammatory immune responses during early stage. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00818 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 24 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Prof. Yaming Cao, China Medical University, Shenyang, China, yamingcao@yahoo.com.cn Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Yonghui Feng Xiaodan Sun Xu Wei Jun Liu Yaming Cao Google Yonghui Feng Xiaodan Sun Xu Wei Jun Liu Yaming Cao Google Scholar Yonghui Feng Xiaodan Sun Xu Wei Jun Liu Yaming Cao PubMed Yonghui Feng Xiaodan Sun Xu Wei Jun Liu Yaming Cao Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Objective To evaluate transcription levels of malaria invasion related molecules of morozolite surface protein-1(MSP-1),apical membrane antigen-1(AMA-1) and 235 kDa rhoptry protein(Py 235) after short-time nitric oxide(NO) donor(NOC 5) treatment.Methods Female BALB/c mice infected with P.yoelii 17XL were inoculated with NOC 5 by intraperitoneal injection.The mature parasite schizonts was enriched and total RNA was extracted from schizonts.The transcription levels of MSP-1,AMA-1 and Py 235 were detected with real-time PCR.Results The transcription levels of MSP-1 and AMA-1 were down-regulated.As a virulence marker,the gene 5054 of Py 235 showed low transcription level.Conclusion The important invasion related molecules of MSP-1 and AMA-1 were inhibited after NO treatment.The parasites adjusted its transcriptional pattern and adapted to the host immune environment.

In cases of human malaria, children suffer very high rates of morbidity and mortality. To analyse the mechanisms involved in age-dependent protection against malaria, we investigated the characterization of immune responses to Plasmodium yoelii 17XNL (P.y 17XNL) in young (3 weeks) and middle-aged (8 months) C57BL/6 mice. In this study, we found that 100% of young mice succumbed to P.y 17XNL infection with higher parasitemia, while middle-aged mice were able to clear blood parasites and no mortality was observed. These observations suggested that the young C57BL/6 mice were susceptible to P.y 17XNL infection, whereas the middle-aged mice were resistant. Cellular analysis revealed that both the numbers of splenic myeloid dendritic cells (mDCs) as well as the expression of DC maturation markers were higher in middle-aged mice than those in young mice. The numbers of IgG1- or IgG2a-secreting B cells increased markedly in middle-aged mice after infection with P.y 17XNL. The dynamic change of the number of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in mice infected with P.y 17XNL was also different between the two groups. In addition, the levels of IFN-gamma and NO increased in both groups during early parasite infection, while there was also an obvious increase in IL-4 production in the infected middle-aged mice. The change in IL-10 levels following infection was consistent with that of the change in the number of Tregs. The survival of middle-aged mice following P.y 17XNL infection was dependent upon the establishment of effective Thl and Th2 responses and a successful switch between Th1 and Th2 responses, as well as appropriate functioning of Tregs.

Malaria infections display variation patterns of clinical course and outcome. Although CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells play an essential role in immune homeostasis, the immune regulatory roles involved in malaria infection remains to be elucidated. Herein, we compared the disparity in Treg cells response during the course of blood stage Plasmodium chabaudi chabaudi AS (P. c chabaudi AS) infection in DBA/2 and BALB/c mice. BALB/c mice initiated a Th1/Th2 profile respond to P. c chabaudi AS infection, but DBA/2 mice failed to control P. c chabaudi AS infection and almost of them died post-peak parasitemia. At the peak parasitemia, we found that higher proportion of Treg cells with elevated Foxp3 expression in DBA/2 than in BALB/c mice. We used anti-CD25 mAb to deplete Treg cells and found that the survival time and rate were prolonged in DBA/2 mice treated with anti-CD25 mAb. Treatment with anti-CD25 mAb in vivo led to enhanced pro-inflammation responses and Foxp3 expression decline on Treg cells. In contrast, after DBA/2 was treatment with anti-IL-10R mAb, IL-10R blockade in vivo caused excessive pro-inflammation responses and Foxp3 expression loss on CD4(+)CD25(+) T cells. Earlier death was found in all of DBA/2 mice with anti-IL-10R mAb. It suggested that IL-2 and IL-10 signal involved in maintaining Foxp3 expression on Treg cells. In all, the moderate suppressive activity of Treg cells may facilitate resistance to P. c chabaudi AS infection.

The modification of proteins by ubiquitination and deubiquitination plays an important role in various cellular processes. BRCA1-associated protein-1 (BAP1) is a deubiquitinating enzyme whose function in the control of the cell cycle requires both its deubiquitinating activity and nuclear localization. In the present study, a ubiquitin carboxyl-terminal hydrolase belonging to the BAP1 family was identified and characterized from Artemia parthenogenetica , a member of a family of brine shrimp that, under certain conditions, produce and release diapause embryos in which cell division and turnover of macromolecules are arrested. Western blot analysis and in vitro enzyme activity assay revealed ArBAP1 to be a cytoplasmic protein with typical ubiquitin hydrolase activity. Northern blot analysis revealed that ArBAP1 was abundant in the abdomen of Artemia producing diapause-destined embryos. Furthermore, by in situ hybridization, ArBAP1 was located exclusively in the embryos. In vivo knockdown of ArBAP1 by RNA interference resulted in the formation of embryos with split shells and abortive nauplii. The present findings suggest that ArBAP1, the first reported cytoplasmic BAP1, participates in the formation of diapause embryos and plays an important role in the control of cell cycle arrest in these encysted embryos.

The effects of NO on the transcription levels of correlated invasive molecules MSP-1,AMA-1,and RhopH complex during Plasmodium erythrocytic stage were investigated.Female BALB/c mice were infected with 1×106 lethal type Plasmodium yoelii 17XL in abdominal cavity,then the mice were treated with long-acting NO(NOC18) and short-acting NO(NOC5) donors in vivo to carry out interference.Mature Plasmodium schizonts were purified and extracted their total RNA.The transcription levels of MSP-1,AMA-1,and RhopH complex were detected by real-time PCR relative quantitative determination.The results showed that the transcription levels of key molecules of MSP-1,AMA-1,and RhopH complex of Plasmodium invasion after treated with NOC5 decreased tangibly as compared with normal infected groups.However,the phenomenon was not seen in the groups treated with NOC18.These result indicated that NO inhibited the transcription levels of Plasmodium invasive key molecules,and proceeded to reduce the expression of Plasmodium corresponding protein,therefore,affected the Plasmodium invasive process.

To investigate the dendritic cells(DCs) subpopulation and phenotype characteristics during early infection of Plasmodium chabaudi chabaudi(AS).The susceptible DBA/2 mice and the resistant BALB/c mice were infected by intraperitoneal injection of 1 106 P.c.chabaudi parasitized erythrocytes.Spleen cell suspension was prepared from the mice sacrificed on days 0,3,5,8 post infection(p.i.).The percentages of myeloid DCs,plasmacytoid DCs,as well as surface molecule MHCII or CD80 expressed on spleen DCs were determined by flow cytometry.The results indicated that DBA/2 mice and BALB/c mice respectively presented myeloid DCs and plasmacytoid DCs dominant proliferation pattern.The expression of MHCⅡand CD80 were significantly increased on days 3-5 p.i.and reached its peak on day 8 p.i.for BALB/c and DBA/2 mice.However,their expression levels in BALB/c mice were significantly lower than that in DBA/2 mice on day 8 p.i..These results indicated that there are significant differences in subpopulation proliferation model and the surface marker expression for DCs in BALB/c and DBA/2 mice during the early stages of P.c.chabaudi infection.