Work

The NLRP12 inflammasome negatively regulates neutrophil function and recruitment during methicillin-resistant staphylococcus aureus (MRSA)-induced pneumonia 2591

Year: 2025

Type: article

Abstract: Description Rationale MRSA is the leading cause of community and hospital-acquired pneumonia. However, the role of NLRP12 during MRSA-induced pneumonia remains elusive. Methods Female wild-type (WT) and NLRP12 knockout (KO) mice were infected with MRSA (USA300, 5 x 107 CFU). We quantified cytokines and chemokines in the bronchoalveolar lavage fluid (BALF) and lung tissues and enumerated bacterial burden in the organs. We performed extracellular bacterial killing assays using bone marrow-derived neutrophils (BMDNs) from WT and KO mice. We also performed infection in mice after bone marrow transplantation. Finally, we depleted neutrophils from WT and KO mice and monitored survival after MRSA infection. Results NLRP12 is upregulated in neutrophils, macrophages, and epithelial cells of both human and murine pneumonic lungs. The KO mice had a higher survival rate than the WT mice, which was associated with lower bacterial burden in the lungs and spleens of the KO mice. The KO mice had higher levels of neutrophils and macrophages as well as cytokines/chemokines (IFN-γ and IL-17A) in BALF. The KO BMDNs are more potent in the extracellular killing of MRSA. Using chimeric mice, the deletion of NLRP12 in the hematopoietic cells increased bacterial clearance in the lungs. Furthermore, neutrophil depletion in the KO mice ameliorated the protection against MRSA pneumonia. Conclusion Deletion of NLRP12 augments neutrophil and macrophage recruitment and increases survival during MRSA pneumonia. Funding Sources Supported by NIH F31HL168986-02, R01AI157353, R01A1180123, and 1RO1AI140500 Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.493

Authors: John Thai Le, Laxman Ghimire, Ky Hoang, Samithamby Jeyaseelan

Institutions: Louisiana State University, Louisiana State University Health Sciences Center Shreveport

Language: English

Topic: Inflammasome and immune disorders

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

OpenAlex ID: W4416446427