Lung disease is rampant around the Salton Sea, California’s largest inland lake and a major source of airborne particulates. To examine root causes of pulmonary disease, we investigated the exposure impacts of spatiotemporal variation in aerosols collected near the Salton Sea on lung and fecal microbiomes. We collected dust during the summer and fall at three different sites around the Salton Sea from 2020 to 2022. Dust was filtered to remove microbial cells and aerosolized for 7-day chronic murine exposures within controlled environmental chambers, after which mouse lung and fecal samples were used for 16S rRNA V3-V4 amplicon sequencing. We verified that chronic exposure to aerosols elicits neutrophilic pulmonary inflammation, particularly in mice exposed to collections from the Wister site near the Salton Sea. We found that spatiotemporal variation drove variation in lung microbiome composition in mice exposed to aerosols from 2022. The lung microbiomes of Salton Sea aerosol-exposed mice were found to increase in alpha-diversity and richness, while simultaneously decreasing in evenness. In contrast, the fecal microbiomes of aerosol-exposed mice decreased in diversity and richness. Our findings suggest that chronic exposure to aerosols from Wister, a site immediately Southeast of the Salton Sea, triggers a systemic stress response in mice characterized by high pulmonary neutrophil recruitment, increased lung microbiome diversity, and decreased fecal microbiome diversity. Back trajectory analyses for aerosol surface type frequencies revealed higher contributions from the Salton Sea in 2020 and 2022 collections from Wister. These findings suggest that chronic exposure to Salton Sea aerosols have impacts on host pulmonary and systemic health, as emphasized by significant but opposing effects on lung and fecal microbiome diversity. Furthermore, these findings demonstrate the variable capacity of environmental aerosol exposure to elicit health consequences relative to seasonal weather events.

Inhalation of dust is significant and relevant to health effects. As pollution and climate change worsen in dryland regions, wind currents entrain loose sediment and dust. This potentially disperses toxic geochemical and microbial burdens throughout the region. When inhaled environmental dust and host-associated microbiomes mingle, they pose exposure risks to host respiratory health. The Salton Sea, California’s largest lake, is shrinking thus exposing nearby communities to playa dust. Therefore, we analyze the effect of Salton Sea dust exposure in murine models to relate lung microbial communities and respiratory health. We used an environmental chamber to expose mice to dust filtrate or ambient air and examined the effects of those exposures on lung microbiomes. We found that lung microbial composition varied by dust exposure. Furthermore, dust elicited neutrophil recruitment and immune responses more than mice exposed to ambient air. Sources of dust differentially affected the composition of the lung core microbiome. Lung microbial diversity correlated with neutrophil recruitment as lungs associated with inflammatory responses harbored more diverse microbiomes. Although Salton Sea dust influences dust microbiomes and prevalent taxa, these responses were variable. The composition of lungs exposed to dust collected further from the Sea was more similar to lungs from ambient air exposures; in contrast, dust collected near the Sea yielded lung microbiomes that clustered further from lungs exposed to ambient air. As lakes continue to dry out, we expect greater public health risks in proximal dryland regions, which may correlate with dust microbial dispersal-related changes to lung microbiomes. Importance Dust inhalation can lead to health effects, especially when toxic chemicals and microbes mix in with the dust particles. As California’s Salton Sea dries up, it exposes lake bottom sediments to wind, which disperses the dried sediments. To mimic the effect of inhaling Salton Sea dust, we collected and filtered airborne dust to use in exposure experiments with mice in environmental chambers. We predicted that inhaling small dust particles, chemicals, and microbial residues found in this dust would affect mouse respiratory health, or change the microbes found inside their lungs. We found that inhaling dust led to lung inflammation and the dust source influenced the type of microbes found inside mouse lungs. As lakes continue to dry out, we expect greater health risks and changes to lung microbiomes. ![Figure][1] [1]: pending:yes

Inhalation of dust is significant and relevant to health effects. As pollution and climate change worsen in dryland regions, wind currents entrain loose sediment and dust. This potentially disperses toxic geochemical and microbial burdens throughout the region. When inhaled environmental dust and host-associated microbiomes mingle, they pose exposure risks to host respiratory health. The Salton Sea, California's largest lake, is shrinking, thus exposing nearby communities to playa dust. Therefore, we analyze the effect of Salton Sea dust exposure in murine models to relate lung microbial communities and respiratory health. We used an environmental chamber to expose mice to dust filtrate or ambient air and examined the effects of those exposures on lung microbiomes. We found that lung microbial composition varied by dust exposure. Furthermore, dust elicited neutrophil recruitment and immune responses more than mice exposed to ambient air. Sources of dust differentially affected the composition of the lung core microbiome. Lung microbial diversity correlated with neutrophil recruitment as lungs associated with inflammatory responses harbored more diverse microbiomes. Although Salton Sea dust influences dust microbiomes and prevalent taxa, these responses are variable. The composition of lungs exposed to dust collected further from the Salton Sea was more similar to lungs from ambient air exposures; in contrast, dust collected near the Salton Sea yielded lung microbiomes that clustered further from lungs exposed to ambient air. As lakes continue to dry out, we expect greater public health risks in proximal dryland regions, which may correlate with dust microbial dispersal-related changes to lung microbiomes. IMPORTANCE:Dust inhalation can lead to health effects, especially when toxic chemicals and microbes mix in with the dust particles. As California's Salton Sea dries up, it exposes lake bottom sediments to wind, which disperses the dried sediments. To mimic the effect of inhaling Salton Sea dust, we collected and filtered airborne dust to use in exposure experiments with mice in environmental chambers. We predicted that inhaling small dust particles, chemicals, and microbial residues found in this dust would affect mouse respiratory health or change the microbes found inside their lungs. We found that inhaling dust led to lung inflammation, and the dust source influenced the type of microbes found inside mouse lungs. As lakes continue to dry out, we expect greater health risks and changes to lung microbiomes.

Background A high incidence of asthma is prevalent among residents near the Salton Sea, a large inland terminal lake in southern California. This arid region has high levels of ambient particulate matter (PM); yet while high PM levels are often associated with asthma in many environments, it is possible that the rapidly retreating lake may contribute components with a specific role in promoting asthma symptoms. Objectives Our hypothesis is that asthma may be higher in residents closest to the Salton Sea due to chronic exposures to playa dust. Playa emissions may be concentrating dissolved material from the lake, with microbial components capable of inducing pulmonary innate immune responses. Such inflammatory responses may contribute to the development of asthma-like symptoms in residents. To test this hypothesis, we used a mouse model of aerosol exposures to assess the effects of playa dust. Methods From dust collected around the Salton Sea region, aqueous extracts were used to generate aerosols, which were injected into an environmental chamber for mouse exposure studies. We compared the effects of exposure to Salton Sea aerosols, as well as to known immunostimulatory reference materials. Acute 48-hour and chronic 7-day exposures were compared, with lungs analyzed for inflammatory cell recruitment and gene expression. Results Dust from sites nearest to the Salton Sea triggered lung neutrophil inflammation that was stronger at 48-hours but reduced at 7-days. This acute inflammatory profile and kinetics resembled the response to innate immune ligands LTA and LPS while distinct from the classic allergic response to Alternaria . Conclusion Lung inflammatory responses to Salton Sea dusts are similar to acute innate immune responses, raising the possibility that microbial components are entrained in the dust, promoting inflammation. This effect highlights the health risks at drying terminal lakes from inflammatory components in dust emissions from exposed lakebed.

Background: A high incidence of asthma is prevalent among residents near the Salton Sea, a large inland terminal lake in southern California. This arid region has high levels of ambient particulate matter (PM); yet while high PM levels are often associated with asthma in many environments, it is possible that the rapidly retreating lake, and exposed playa or lakebed, may contribute components with a specific role in promoting asthma symptoms.Objectives: Our hypothesis is that asthma may be higher in residents closest to the Salton Sea due to chronic exposures to playa dust. Playa emissions maybe concentrating dissolved material from the lake, with microbial components capable of inducing pulmonary innate immune responses. To test this hypothesis, we used a mouse model of aerosol exposures to as-sess the effects of playa dust.Methods: From dust collected around the Salton Sea region, aqueous extracts were used to generate aerosols, which were injected into an environmental chamber for mouse exposure studies. We compared the effects of exposure to Salton Sea aerosols, as well as to known immunostimulatory reference materials. Acute 48-h and chronic 7-day exposures were com-pared, with lungs analyzed for inflammatory cell recruitment and gene expression.Results: Dust from sites nearest to the Salton Sea triggered lung neutrophil inflammation that was stronger at 48-h but re-duced at 7-days. This acute inflammatory profile and kinetics resembled the response to innate immune ligands LTA and LPS while distinct from the classic allergic response to Alternaria.Conclusion: Lung inflammatory responses to Salton Sea dusts are similar to acute innate immune responses, raising the pos-sibility that microbial components are entrained in the dust, promoting inflammation. This effect highlights the health risks at drying terminal lakes from inflammatory components in dust emissions from exposed lakebed.

The Salton Sea is a drying salt lake in an arid region with high aerosol particulate-matter concentrations. This region is plagued by a high incidence of asthma, attributed in part to the aerosols surrounding the Sea. But the connection between the Sea and asthma may be more than simple calculations of dust concentrations. While dusts might contain toxic substances that impact the lungs of residents, the complex dynamics related to the environmental degradation of the Salton Sea may be generating additional toxins relevant to public health, such as microcystins produced by algal blooms. This collection of pollutants may be driving inflammatory responses in the lungs of residents through multiple mechanisms. As such, examination of the full range of potential environmental triggers of lung inflammation promises to yield a better understanding of key mechanisms driving the high incidence of asthma in local residents. Our discussion provides a perspective aiming to re-frame the issue in the context of the historical theory of “miasma” and the linkages between environmental change and health impacts.

Bacterial growth and division are extensively studied in model systems ( Escherichia coli , Bacillus subtilis , and Caulobacter crescentus ) that grow by dispersed insertion of new cell wall material along the length of the cell. An alternative growth mode—polar growth—is used by some Actinomycetales and Proteobacteria species.

In communities surrounding the Salton Sea, high rates of asthma are associated with high aerosol dust levels. However, the Salton Sea itself may play an additional role in pulmonary health. Therefore, to investigate a potential role of the Salton Sea on pulmonary health, we exposed mice to aerosolized Salton Sea water for 7 days and assessed tissue responses, including cellular infiltration and gene expression changes. For reference, mice were also exposed to aerosolized fungal allergen (Alternaria sp.) and Pacific Ocean aerosols. Exposure to aerosolized Alternaria sp. induced dramatic allergic inflammation, including neutrophil and eosinophil recruitment to the bronchoalveolar lavage fluid (BALF) and lung tissue. By contrast, Salton Sea “spray” induced only B cell recruitment to the lung tissue without increased inflammatory cell numbers in BALF. However, there were consistent gene expression changes suggestive of an inflammatory response. The response to the Salton Sea spray was notably distinct from the response to Pacific Ocean water, which induced some B cell recruitment but without an inflammatory gene expression profile. Our studies suggest that soluble components in Salton Sea water promote induction of a unique inflammation-associated response, though any relationship to asthma remains to be explored.

BG505 SOSIP is a well-characterized near-native recombinant HIV Envelope (Env) trimer that holds promise as part of a sequential HIV immunogen regimen to induce broadly neutralizing antibodies (bnAbs). Rhesus macaques are considered the most appropriate pre-clinical animal model for monitoring antibody (Ab) responses. Accordingly, we report here the isolation of 45 BG505 autologous neutralizing antibodies (nAbs) with multiple specificities from SOSIP-immunized and BG505 SHIV-infected rhesus macaques. We associate the most potent neutralization with two epitopes: the C3/V5 and V1/V3 regions. We show that all of the nAbs bind in close proximity to known bnAb epitopes and might therefore sterically hinder elicitation of bnAbs. We also identify a "public clonotype" that targets the immunodominant C3/V5 nAb epitope, which suggests that common antibody rearrangements might help determine humoral responses to Env immunogens. The results highlight important considerations for vaccine design in anticipation of results of the BG505 SOSIP trimer in clinical trials.

Implanted medical device-associated infections pose significant health risks, as they are often the result of bacterial biofilm formation. Staphylococcus aureus is a leading cause of biofilm-associated infections which persist due to mechanisms of device surface adhesion, biofilm accumulation, and reprogramming of host innate immune responses. We found that the S. aureus fibronectin binding protein A (FnBPA) is required for normal biofilm development in mammalian serum and that the SaeRS two-component system is required for functional FnBPA activity in serum. Furthermore, serum-developed biofilms deficient in FnBPA were more susceptible to macrophage invasion, and in a model of biofilm-associated implant infection, we found that FnBPA is crucial for the establishment of infection. Together, these findings show that S. aureus FnBPA plays an important role in physical biofilm development and represents a potential therapeutic target for the prevention and treatment of device-associated infections.

The VH1-2 restricted VRC01-class of antibodies targeting the HIV envelope CD4 binding site are a major focus of HIV vaccine strategies. However, a detailed analysis of VRC01-class antibody development has been limited by the rare nature of these responses during natural infection and the lack of longitudinal sampling of such responses. To inform vaccine strategies, we mapped the development of a VRC01-class antibody lineage (PCIN63) in the subtype C infected IAVI Protocol C neutralizer PC063. PCIN63 monoclonal antibodies had the hallmark VRC01-class features and demonstrated neutralization breadth similar to the prototype VRC01 antibody, but were 2- to 3-fold less mutated. Maturation occurred rapidly within ∼24 months of emergence of the lineage and somatic hypermutations accumulated at key contact residues. This longitudinal study of broadly neutralizing VRC01-class antibody lineage reveals early binding to the N276-glycan during affinity maturation, which may have implications for vaccine design.