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Lung Epithelial Regnase-1 Dampens Local Immune Response but Does Not Worsen Susceptibility to Klebsiella pneumoniae.
Lin, Becky; Fan, Li; Jackson, Shaterra; Matunis, Aidan R; Lou, Dequan; Chen, Kong; Trevejo-Nuñez, Giraldina.
Afiliação
  • Lin B; Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA.
  • Fan L; Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.
  • Jackson S; Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA.
  • Matunis AR; Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA.
  • Lou D; Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.
  • Chen K; Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.
  • Trevejo-Nuñez G; Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA.
Immunohorizons ; 8(1): 89-96, 2024 Jan 01.
Article em En | MEDLINE | ID: mdl-38226923
ABSTRACT
Klebsiella pneumoniae (KP) presents a global health threat, leading to significant morbidity and mortality due to its multidrug-resistant profile and the limited availability of therapeutic options. To eliminate KP lung infection, the host initiates a robust inflammatory response. One of the host's mechanisms for mitigating excessive inflammation involves the RNA-binding protein regnase-1 (Reg1, MCPIP1, or ZC3H12A). Reg1 has an RNA binding domain that recognizes stem-loop structures in the 3' untranslated region of various proinflammatory transcripts, leading to mRNA decay. However, excessive suppression of inflammation by Reg1 results in suboptimal KP control. Reg1 deficiency within the nonhematopoietic compartment confers resistance to KP in the lung. Given that lung epithelium is crucial for KP resistance, we hypothesized that selective deletion of Reg1 in lung epithelial cells might enhance proinflammatory signals, leading to a better control of KP. Our transcriptomic analysis of epithelial cells in KP-infected wild-type mice revealed the presence of three distinct alveolar type 2 cell (AT2) subpopulations (conventional, inflammatory, and cycling) and enrichment of Reg1 in inflammatory AT2 cells. We conditionally deleted Reg1 in lung AT2 cells (ΔReg1), which amplified the local inflammatory response in the lung and increased macrophage cell numbers compared with controls. However, when ΔReg1 mice were subjected to KP infection, there were no significant differences in bacterial burden or survival compared with controls. These findings suggest that the local inflammatory response enhanced by Reg1 deletion in AT2 cells is insufficient to control KP infection.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ribonucleases / Células Epiteliais / Klebsiella pneumoniae Limite: Animals Idioma: En Revista: Immunohorizons Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ribonucleases / Células Epiteliais / Klebsiella pneumoniae Limite: Animals Idioma: En Revista: Immunohorizons Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos