Noncanonical T cell responses are associated with protection from tuberculosis in mice and humans

• DOI: 10.1084/jem.20241760
• Publication Date: 2025-04-07T13:51:33Z
• Authors: Megan K. Proulx; Christine D. Wiggins; Charlotte J. Reames; Claire Wu; Michael C. Kiritsy; Ping Xu; Judith C. Gallant; Patricia S. Grace; Brooke A. Fenderson; Clare M. Smith; Cecilia S. Lindes...; Galit Alter; Douglas A. Lauffe...; Christopher M. Sa...

While control of Mycobacterium tuberculosis (Mtb) infection is generally understood to require Th1 cells and IFNγ, produces a spectrum immunological pathological phenotypes in diverse human populations. By characterizing Mtb mouse strains that model the genetic heterogeneity an outbred population, we identified comparably standard IFNγ-dependent but with substantially lower lung IFNγ levels. We report these mice have significantly altered CD4 T cell profile specifically lacks terminal effector subset this phenotype detectable before infection. These still bacterial burden are less dependent on signaling. Instead, noncanonical immune features such as Th17-like γδT correlate low burden. find same Th17 transcriptional programs associated resistance humans, implicating specific non-Th1 responses common feature across species.