Nuclear Factor κB Signaling Deficiency in CD11c-Expressing Phagocytes Mediates Early Inflammatory Responses and Enhances Mycobacterium tuberculosis Control

Kuldeep S. Chauhan, Micah D. Dunlap, Sadia Akter, Ananya Gupta, Mushtaq Ahmed, Bruce A. Rosa, Noreen B. Dela Peña, Makedonka Mitreva, Shabaana Abdul Khader

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Early innate immune responses play an important role in determining the protective outcome of Mycobacterium tuberculosis (Mtb) infection. Nuclear factor κB (NF-κB) signaling in immune cells regulates the expression of key downstream effector molecules that mount early antimycobacterial 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 the absence of IKK2-mediated signaling in all myeloid cells resulted in increased susceptibility to Mtb infection. In contrast, the absence of IKK2-mediated signaling in CD11c+ myeloid cells induced early proinflammatory cytokine responses, enhanced the recruitment of myeloid cells, and mediated early resistance to Mtb. Abrogation of IKK2 in MRP8-expressing neutrophils did not affect 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.

Original languageEnglish
Pages (from-to)336-345
Number of pages10
JournalJournal of Infectious Diseases
Volume230
Issue number2
DOIs
StatePublished - Aug 15 2024

Keywords

  • immune regulation
  • inflammation
  • innate immunity
  • Mycobacterium tuberculosis
  • NF-κB pathway

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