Toll-like receptors (TLRs) are pattern-recognition receptors-reported primarily on antigen-presenting cells-recognizing pathogen-associated molecular patterns and triggering effector immune responses (Chauhan et al., 2017). T-cells also express TLRs in both mice and humans (Nouri et al., 2021). Signals through TLRs alone are sufficient to moderate the functions of macrophages and dendritic cells (Chauhan et al., 2017). As the levels of TLRs expression in T-cells is substantially less, the T-cell expressed TLRs appear ancillary to the T-cell receptor (TCR)-triggered effector functions such that the TLR-triggered costimulatory effects are only visible in case of simultaneous TCR stimulation (Flaherty and Reynolds, 2016). Till date, TLR2, TLR7 and TLR9 have been implicated in modulating T-cell functions, in particular, providing signals secondary to TCR and modulating T-cell proliferation, cytokine production and survival (Nouri et al., 2021). TLR2 can form heterodimers with either TLR1,recognizing triacylated lipopeptides, or TLR6, binding diacylated lipopeptides; depending on the partner TLR- TLR1 or TLR6, TLR2 exhibits duality in its signaling and elicits either anti-inflammaotry or pro-inflammatory functions, respectively, in macrophages (Chauhan et al., 2017; Pandey et al., 2014). TLR2 ligands downregulate TLR9, but upregulate TLR11, expression in BALB/c-derived macrophages (Shukla et al., 2021) whereas TLR9 is shown to cross-talk with CD40 up-regulating each other's expression in mouse macrophages (Chandel et al., 2014). By way of this cross-talk, CD40 and TLR9 synergizes cytokine production and anti-leishmanial funcitons (Chandel et al., 2014). These results suggest that pathogens such as Mycobacteria, Salmonella or Leishmania that infect macrophages may modulate these TLRs expression in a co-ordinated manner to regulate the T-cell-dependent immune response (Chandel et al., 2014; Chauhan et al., 2017; Lancioni et al., 2011; Pandey et al., 2014; Reynolds and Dong, 2013; Shukla et al., 2021). However, whether any of these infections affects TLRs' expression and function on T-cells has never been addressed.

T-cells express multiple TLRs that may play co-regulatory roles in TCR-activated T-cells (Flaherty and Reynolds, 2016) and differentially in hepatitis C virus (HCV) infection (Hammond et al., 2010). However, the expression of all TLRs in T-cells awaits systematic analyses such that the expression of all TLRs on T cells-probed by using different fluorochromes-labeled antibodies against all TLRs-is studied. Most experiments involved studying only one or two TLRs on T cells. Therefore, using fluorochorme-labelled antibodies against all TLRs, we analyzed the expression of all TLRs in CD4+ and CD8+ T-cells from uninfected and Leishmania-infected BALB/c mice (Supplementary table-1). We assessed whether the expression of these TLRs associated with effector CD4+T-cell subsets, which might play crucial roles in this protozoan parasite infection (Jafarzadeh et al., 2022; Kaye, 1995). Although Leishmania does not infect T-cells, the data presented here show altered expression of TLRs on T-cells in L. donovani-infected BALB/c mice, a Leishmania-susceptible mammalian host.