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Nuclear Factor κB Signaling Deficiency in CD11c-Expressing Phagocytes Mediates Early Inflammatory Responses and Enhances Mycobacterium tuberculosis Control.
- Source :
-
The Journal of infectious diseases [J Infect Dis] 2024 Aug 16; Vol. 230 (2), pp. 336-345. - Publication Year :
- 2024
-
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.<br />Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.<br /> (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Animals
Mice
I-kappa B Kinase metabolism
I-kappa B Kinase genetics
Mice, Inbred C57BL
Inflammation metabolism
Inflammation immunology
Cytokines metabolism
Neutrophils immunology
Neutrophils metabolism
CD11 Antigens
Mycobacterium tuberculosis immunology
NF-kappa B metabolism
Signal Transduction
Phagocytes immunology
Phagocytes metabolism
Mice, Knockout
Tuberculosis immunology
Tuberculosis microbiology
CD11c Antigen metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6613
- Volume :
- 230
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 38324907
- Full Text :
- https://doi.org/10.1093/infdis/jiae060