<i>Leishmania major</i> co-opts IL-7 feedback in monocytes to suppress CD4⁺ T-cell immunity

Summary Effective immunity against infections requires a tight balance between pro- and anti-inflammatory pathways to ensure pathogen clearance while preserving tissue integrity. Intracellular pathogens such as Leishmania major can exploit host-cell immunosuppressive functions, yet the underlying molecular and cellular interactions remain incompletely understood. Here we report a monocyte-derived, hypo-inflammatory PDPN⁺IL-7R⁺ subset that harbours low-proliferating parasites, inhibits effector CD4⁺ T-cell control of intracellular pathogens, and therefore perpetuates infection. This immunosuppression is mediated by fibroblast-derived IL-7, which is up-regulated in response to IFNγ. Thus, our data suggest a cytokine-dependent feedback switch through which IL-7 activates immunosuppressive monocyte-derived cells when local IFNγ production exceeds a critical level. This dampens effector CD4 + T cell functions at the expense of pathogen persistence. Targeting this feedback loop may yield novel immunotherapeutic strategies that enhance immune responses while maintaining tissue integrity.