NLRP12 modulates host defense through IL-17A-CXCL1 axis

Mucosal Immunology
Shanshan CaiSamithamby Jeyaseelan

Abstract

We used an extracellular pathogen Klebsiella pneumoniae to determine the role of NLRP12 (NOD-like receptor (NLR) family pyrin domain containing 12) as this bacterium is associated with devastating pulmonary infections. We found that human myeloid cells (neutrophils and macrophages) and non-myeloid cells (epithelial cells) show upregulation of NLRP12 in human pneumonic lungs. NLRP12-silenced human macrophages and murine Nlrp12(-/-) macrophages displayed reduced activation of nuclear factor-κB and mitogen-activated protein kinase, as well as expression of histone deacetylases following K. pneumoniae infection. NLRP12 is important for the production of interleukin-1β (IL-1β) in human and murine macrophages following K. pneumoniae infection. Furthermore, host survival, bacterial clearance, and neutrophil recruitment are dependent on NLRP12 following K. pneumoniae infection. Using bone marrow chimeras, we showed that hematopoietic cell-driven NLRP12 signaling predominantly contributes to host defense against K. pneumoniae. Intratracheal administration of either IL-17A+ CD4 T cells or chemokine (C-X-C motif) ligand 1 (CXCL1+) macrophages rescues host survival, bacterial clearance, and neutrophil recruitment in Nlrp12(-/-) mice follow...Continue Reading

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Citations

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Aug 4, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tirumalai RangasamySamithamby Jeyaseelan

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Methods Mentioned

BETA
bronchoalveolar lavage
bronchoalveolar
lavage
Transfection
light microscopy
ELISA
flow cytometry

Software Mentioned

GraphPad Prizm
InStat

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