Biology subjects

Maity, H. K.

Publications and source records attributed to Maity, H. K..

3 recordsLinked to original sources

bioRxiv2024

Transcriptomic profiling identifies breed-specific immune signatures of Tuberculosis susceptibility in cattle

Tuberculosis (TB) remains a major chronic infectious disease in cattle, particularly challenging in India which hosts the worlds largest and most diverse cattle population farmed in close proximity to its human settlements. This study investigates the hypothesis that genetic and immune variations drive differential TB susceptibility in cattle breeds. Using comprehensive transcriptomic analyses, we examined immune responses in peripheral blood mononuclear cells (PBMCs) from Sahiwal and Sahiwal-Holstein Friesian (SHF) crossbred cattle. Responses to both the virulent Mycobacterium tuberculosis and the vaccine strain M. bovis BCG were compared. Notably, Sahiwal cattle exhibited a robust early immune response characterized by upregulation of interferon signaling, enhanced cytotoxic activity by CD8+ T and NK cells, and pronounced T cell recruitment and activation pathways compared to SHF crossbreds. PBMCs of this breed also demonstrated superior control of M. tuberculosis replication in vitro. A distinctive immune signature comprising 8 genes, including CXCL10, ISG15, CTLA4, SELL, TLR3, MYD88, IRF1, and EOMES was significantly upregulated in Sahiwal cattle PBMCs, potentially driving their reduced TB susceptibility. These findings underscore the importance of breed-specific immune profiling in devising effective TB control strategies, and could lead to targeted interventions that leverage genetic and immunological insights to mitigate TB in regions with high cattle diversity.

systems biology↗

bioRxiv2023

A bovine pulmosphere model and multiomics analyses identify a signature of early host response to Mycobacterium tuberculosis infection

Interactions between the tubercle bacilli and lung cells during the early stages of tuberculosis (TB) are crucial for disease outcomes. Conventional 2D cell culture inadequately replicates the multicellular complexity of lungs. We introduce a 3D pulmosphere model for Mycobacterium tuberculosis infection in bovine systems, demonstrating through comprehensive transcriptome and proteome analyses that these 3D structures closely replicate the diverse cell populations and abundant extracellular matrix proteins, emphasizing their similarity to the in vivo pulmonary environment. While both avirulent BCG and virulent M. tuberculosis-infected pulmospheres exhibit commonalities in the upregulation of several host signaling pathways, distinct features such as upregulation of ECM receptors, neutrophil chemotaxis, interferon signaling, and RIG-1 signaling pathways characterize the unique early response to virulent M. tuberculosis. Moreover, a signature of seven genes/proteins, including IRF1, CCL5, CXCL8, CXCL10, ICAM1, COL17A1, and CFB, emerges as indicative of the early host response to M. tuberculosis infection. Overall, this study presents a superior ex vivo multicellular bovine pulmosphere TB model, with implications for discovering disease biomarkers, enabling high-throughput drug screening, and improving TB control strategies.

systems biology↗

bioRxiv2023

Divergent proinflammatory immune responses associated with the differential susceptibility of cattle breeds to Tuberculosis

Tuberculosis (TB) in the bovine is one of the most predominant chronic debilitating infectious diseases primarily caused by Mycobacterium bovis. Besides, the incidence of TB in humans due to M. bovis, and that in bovines due to M. tuberculosis-indicates cattle as a major reservoir of zoonotic TB. While India accounts for the highest global burden of both TB and multidrug-resistant TB in humans, systematic evaluation of bovine TB (bTB) prevalence in India is largely lacking. Recent reports emphasized markedly greater bTB prevalence in exotic and crossbred cattle compared to indigenous cattle breeds that represent more than one-third of the total cattle population in India, which is the largest globally. This study aimed at elucidating the immune responses underlying the differential bTB incidence in prominent indigenous (Sahiwal), and crossbred (Sahiwal x Holstein Friesian) cattle reared in India. Employing the standard Single Intradermal Tuberculin Test (SITT), and mycobacterial gene-targeting single as well as multiplex-PCR-based screening revealed higher incidences of bovine tuberculin reactors as well as Mycobacterium tuberculosis Complex specific PCR positivity amongst the crossbred cattle. Further, ex vivo mycobacterial infection in cultures of bovine peripheral blood mononuclear cells (PBMC) from SITT, and myco-PCR negative healthy cattle exhibited significantly higher intracellular growth of M. bovis BCG, and M. tuberculosis H37Ra in the crossbred cattle PBMCs compared to native cattle. In addition, native cattle PBMCs induced higher pro-inflammatory cytokines and signaling pathways, such as interferon-gamma (IFN-{gamma}), interleukin-17 (IL-17), and tank binding kinase-1 (TBK-1) upon exposure to live mycobacterial infection in comparison to PBMCs from crossbred cattle that exhibited higher expression of IL-1{beta} transcripts. Together, these findings highlight that differences in the innate immune responses of these cattle breeds might be contributing to the differential susceptibility to TB infection, and the resultant disparity in bTB incidence amongst indigenous, and crossbred cattle.

immunology↗