Biology subjects

Shah, V. S.

Publications and source records attributed to Shah, V. S..

3 recordsLinked to original sources

bioRxiv2026

Induced microfold cells are required for the function of pulmonary tertiary lymphoid organs that promote mucosal immunity

Tertiary lymphoid organs (TLOs) arise in response to infection and inflammation. We show that influenza-induced lung TLOs are comprised of inducible M cell (iM cell)-inducible bronchus-associated lymphoid tissue (iBALT) functional composites. iM cells are necessary for the appropriate architecture of adjacent immune follicles, which contain clonally expanded and sequence-diversified B cells. iM cell ablation results in fewer antigen-specific germinal center B cells, T follicular helper cells, and T helper memory cells, and a decrease in secretory IgA and IgG production accompanied by a loss of viral control. We find that the iM cells arise from epithelial progenitors that respond to a RANKL signal from infiltrating T cells, consistent with a model in which the patchy inflammation typical of pneumonia results in the unpredictable and varying distribution of coupled iM cells and adjacent iBALT. We propose that iM cells could be harnessed to promote infection control and enhance mucosal vaccination.

immunology↗

bioRxiv2024

Single-cell analysis of human airway epithelium identifies cell type-specific responses to Aspergillus and Coccidioides

Respiratory fungal infections pose a significant threat to human health. Animal models do not fully recapitulate human disease, necessitating advanced models to study human-fungal pathogen interactions. In this study, we utilized primary human airway epithelial cells (hAECs) to recapitulate the lung environment in vitro and investigate cellular responses to two diverse, clinically significant fungal pathogens, Aspergillus fumigatus and Coccidioides posadasii. To understand the mechanisms of early pathogenesis for both fungi, we performed single-cell RNA sequencing of infected hAECs. Analysis revealed that both fungi induced cellular stress and cytokine production. However, the cell subtypes affected and specific pathways differed between fungi, with A. fumigatus and C. posadasii triggering protein-folding-related stress in ciliated cells and hypoxia responses in secretory cells, respectively. This study represents one of the first reports of single-cell transcriptional analysis of hAECs infected with either A. fumigatus or C. posadasii, providing a vital dataset to dissect the mechanism of disease and potentially identify targetable pathways. ImportanceFungal infections in the lungs are dreaded complications for those with compromised immune systems and have limited treatment strategies available. These options are restricted further by the increased prevalence of treatment-resistant fungi. Many studies focus on how our immune systems respond to these pathogens, yet airway epithelial cells remain an understudied component of fungal infections in the lungs. Here, the authors provide a transcriptional analysis of primary human airway epithelial cells stimulated by two distinct fungal pathogens, Aspergillus fumigatus and Coccidioides posadasii. These data will enable further mechanistic studies of the contribution of the airway epithelium to initial host responses and represent a powerful new resource for investigators.

immunology↗

bioRxiv2020

Structure of the extracellular region of the bacterial type VIIb secretion system subunit EsaA

Gram-positive bacteria use type VII secretion systems (T7SSs) to export effector proteins that manipulate the physiology of nearby prokaryotic and eukaryotic cells. Several mycobacterial T7SSs have established roles in virulence. By contrast, recent work has demonstrated that the genetically distinct T7SSb pathway found in Firmicutes bacteria more often functions to mediate interbacterial competition. A lack of structural information on the T7SSb has limited the understanding of effector export by this protein secretion apparatus. In this work, we present the 2.4[A] crystal structure of the extracellular region of the elusive T7SSb subunit EsaA from Streptococcus gallolyticus. Our structure reveals that homodimeric EsaA is an elongated, arrow-shaped protein with a surface-accessible tip, which serves as a receptor for lytic bacteriophages in some species of bacteria. Because it is the only T7SSb subunit large enough to traverse the thick peptidoglycan layer of Firmicutes bacteria, we propose that EsaA plays a critical role in transporting effectors across the entirety of the Gram-positive cell envelope.

microbiology↗