Mycobacterium avium is a slow-growing non-tuberculous mycobacterium. While its medical importance is increasing, its virulence is only poorly characterized. A highly virulent M. avium strain ATTC25291 (MAA25291) has been shown to cause severe disease in mice by survival and growth in nitric oxide (NO) producing, immune suppressive monocytic-MDSC (M-MDSC). The induction and persistence of MAA25291 in M-MDSC is still unresolved. In the present study, we were interested in the role of M-MDSC in mice infected with MAA25291 at infection doses that led to the manifestation of clinical disease (high dose) or subclinical disease (low dose). Flow cytometry revealed the presence of M-MDSC in both infection groups, however, this infiltration was significantly lower after low dose infection. Histopathology showed lower infiltration of NOS2 expressing cells in spleen and liver correlated with high CD3+ T cell numbers after low dose infection, whereas high dose infection of mice led to T cell losses in the tissues. This study highlights that the infection dose significantly affects M-MDSC induction and their immune regulatory roles. Furthermore, it suggests that the induction and persistence of MAA25291 in M-MDSC relies on the amount of NO production.
Pathogenic Leptospira spp. evade the complement system by capturing soluble regulators of the alternative, classical, and lectin pathways - such as factor H, C4BP, and vitronectin - via proteins on their surface. By capturing these regulators, Leptospira can disrupt the complement activation cascade, thereby preventing opsonization by C3b/iC3b and lysis by the membrane attack complex (MAC). The ability of low-passage pathogenic Leptospira strains - LOCaS46 (L. interrogans sv Canicola), LOVe30 (L. interrogans sv Icterohaemorrhagiae), and MOCA45 (L. santarosai sv Tarassovi) - to bind C4BP was evaluated and compared to their corresponding culture-attenuated (LOCaS46, LOVe30, and MOCA45) and to the saprophytic Patoc I strain of Leptospira biflexa sv Patoc. Binding to C4BP was assessed by ELISA and confirmed by Western blot, the expression level of the genes for C4BP-binding proteins was evaluated by RT-qPCR, and the survival of the Leptospira spp. strains in normal human serum (NHS) was estimated to assess complement resistance. Results showed that culture attenuated (CA) strains had a lower capacity for binding to C4BP, and surviving to NHS as compared to low-passage (LP) strains. Also, transcription level of the genes for the C4BP-binding proteins LigA, LigB, LcpA, enolase and Lsa23, was lower in the CA strains than in their corresponding LP strains. This suggest that reduction of the ability to capture C4BP in culture attenuated (CA) strains is due at least in part to lower expression of C4BP-binding proteins, affecting the evasion of classical and lectin pathways of the complement system and therefore the capability of survival in NHS.
Background Cathepsin play a crucial role in the progression of various diseases, including cancer, neurodegenerative disorders, and processes involving inflammation and immune modulation. The global pandemic of COVID-19 has heightened the need for further exploration into the interactions between cathepsin and the virus, and their impact on disease progression. Methods This study employed Mendelian randomization to analyze the causal relationships between specific genetically predicted plasma cathepsin and COVID-19 outcomes, both severe and non-severe. Using data from genome-wide association studies, we evaluated the associations of genetically predicted plasma levels of cathepsin B, D, F, and S with susceptibility to and severity of COVID-19. Results An increase in genetically predicted circulating cathepsin S levels might be associated with a reduced susceptibility risk to COVID-19 (P < 0.05). Furthermore, while there appears to be a correlation where increased susceptibility to COVID-19 leads to elevated levels of genetically predicted circulating cathepsin F and a reduction in genetically predicted cathepsin S levels (P < 0.05), these associations should be interpreted with caution. There is also suggestive evidence of a causal association between the progression of COVID-19 severity and increased levels of genetically predicted circulating cathepsin F (P < 0.05). However, due to the inherent limitations of the Mendelian randomization approach, further studies are warranted to substantiate these initial findings. Conclusion This study highlights the potential role of cathepsin in the pathophysiology of COVID-19 and suggests that modulating the expression or activity of these enzymes could influence susceptibility and disease severity. These findings provide a new perspective on the interaction between genetically predicted plasma cathepsin and COVID-19, suggesting further research is needed to explore the mechanisms behind these findings and the potential efficacy of interventions targeting specific cathepsin in the prevention or treatment of COVID-19.
This study aims to compare the clinical, laboratory, and therapeutic outcomes between acute and subacute/chronic phases of brucellosis and to identify independent predictors of a favorable treatment response. This retrospective observational and analytic study included 171 patients with brucellosis, categorized as acute (n = 146) or subacute/chronic (n = 25). A therapeutic response was defined as the complete resolution of initial symptoms with no relapse during a 12-month follow-up. A serological response was defined as a ≥4-fold decrease in the serum tube agglutination (STA) titer post-treatment. Outcomes were compared using appropriate statistical tests (p < 0.05), and logistic regression was used to identify predictors of response. Compared to the subacute/chronic group, patients with acute brucellosis had a significantly higher frequency of leukopenia (21.2 % vs. 0 %; p < 0.01), elevated C reactive protein (CRP) (76.7 % vs. 52.0 %; p = 0.01), and elevated transaminases (43.8 % vs. 20.0 %; p = 0.025). A significantly higher therapeutic response rate was observed in acute cases (93.2 %) compared to subacute/chronic cases (0.76 %) (p = 0.01). Multivariate analysis identified elevated baseline CRP (OR: 4.00; p = 0.02) and a post-treatment decrease in STA titer (OR: 5.84; p = 0.007) as independent predictors of a favorable therapeutic response. In conclusion, acute brucellosis presents with a more pronounced inflammatory profile than subacute/chronic forms. While patients with acute brucellosis demonstrated a significantly higher therapeutic response rate, the serological response was also more pronounced in this group. Elevated CRP at diagnosis and a significant decrease in STA titer post-treatment are strong, independent predictors of successful outcomes, highlighting their value in patient monitoring.
