CD14 signaling mediates lung immunopathology and mice mortality induced by Achromobacter xylosoxidans

Resumo

Objective and design Our research aimed to investigate the role of CD14 in pulmonary infection by Achromobacter xylosoxidans in an experimental murine model. Methods C57Bl/6 or CD14-defcient mice were infected intratracheally with non-lethal inoculum of A. xylosoxidans. At times 1, 3 and 7 days after infection, lungs, bronchoalveolar lavage and blood were collected. CD14 gene expression was determined by RT-PCR. The bacterial load in the lungs was assessed by counting colony forming units (CFU). Cytokines, chemokines, lipocalin-2 and sCD14 were quantifed by the ELISA method. Infammatory infltrate was observed on histological sections stained with HE, and leukocyte subtypes were assessed by fow cytometry. In another set of experiments, C57Bl/6 or CD14- defcient mice were inoculated with lethal inoculum and the survival rate determined. Results CD14-defcient mice are protected from A. xylosoxidans-induced death, which is unrelated to bacterial load. The lungs of CD14-defcient mice presented a smaller area of tissue damage, less neutrophil and macrophage infltration, less pulmonary edema, and a lower concentration of IL-6, TNF-α, CXCL1, CCL2 and CCL3 when compared with lungs of C57Bl/6 mice. We also observed that A. xylosoxidans infection increases the number of leukocytes expressing mCD14 and the levels of sCD14 in BALF and serum of C57Bl/6-infected mice. Conclusions In summary, our data show that in A. xylosoxidans infection, the activation of CD14 induces intense pulmonary infammatory response resulting in mice death.

Descrição

Palavras-chave

Achromobacter xylosoxidans, CD14, Soluble CD14, Pneumonia

Citação

ELIAS-OLIVEIRA, Jefferson et al. CD14 signaling mediates lung immunopathology and mice mortality induced by Achromobacter xylosoxidans. Inflammation Research, Basel, v. 71, n. 12, p. 1535-1546, 2022. DOI: 10.1007/s00011-022-01641-8. Disponível em: https://link.springer.com/article/10.1007/s00011-022-01641-8. Acesso em: 29 jan. 2025.