RESUMO
Early innate immune responses play an important role in determining the protective outcome of Mycobacterium tuberculosis (Mtb) infection. Nuclear factor kappa B (NF-κB) signaling in immune cells regulates the expression of key downstream effector molecules that mount early anti-mycobacterial responses. Using conditional knockout mice, we studied the effect of abrogation of NF-κB signaling in different myeloid cell types and its impact on Mtb infection. Our results show that absence of IKK2-mediated signaling in all myeloid cells resulted in increased susceptibility to Mtb infection. In contrast, absence of IKK2-mediated signaling specifically in CD11c+ myeloid cells induced early pro-inflammatory cytokine responses, enhanced the recruitment of myeloid cells and mediated early resistance to Mtb. Abrogation of IKK2 in MRP8-expressing neutrophils did not impact either disease pathology or Mtb control. Thus, we describe an early immunoregulatory role for NF-κB signaling in CD11c-expressing phagocytes, and a later protective role for NF-κB in LysM-expressing cells during Mtb infection.
