NF-κB signaling deficiency in CD11c-expressing phagocytes mediates early inflammatory responses and enhances Mycobacterium tuberculosis control

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 respons...

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Bibliographic Details
Published in:The Journal of infectious diseases 2024-02
Main Authors: Chauhan, Kuldeep S, Dunlap, Micah D, Akter, Sadia, Gupta, Ananya, Ahmed, Mushtaq, Rosa, Bruce A, Dela Peña, Noreen B, Mitreva, Makedonka, Khader, Shabaana A
Format: Article
Language:English
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Summary: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.
ISSN:1537-6613