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

Abstract

AbstractTuberculosis (TB) in the bovine is one of the most predominant chronic debilitating infectious diseases primarily caused byMycobacterium bovis. Besides, the incidence of TB in humans due toM. bovis, and that in bovines due toM. 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 asMycobacterium tuberculosisComplex specific PCR positivity amongst the crossbred cattle. Further,ex vivomycobacterial infection in cultures of bovine peripheral blood mononuclear cells (PBMC) from SITT, and myco-PCR negative healthy cattle exhibited significantly higher intracellular growth ofM. bovisBCG, andM. tuberculosisH37Ra 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-γ), 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-1β 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.