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

Abstract

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-deficient 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 quantified by the ELISA method. Inflammatory infiltrate was observed on histological sections stained with HE, and leukocyte subtypes were assessed by flow cytometry. In another set of experiments, C57Bl/6 or CD14-deficient mice were inoculated with lethal inoculum and the survival rate determined. Results CD14-deficient mice are protected from A. xylosoxidans -induced death, which is unrelated to bacterial load. The lungs of CD14-deficient mice presented a smaller area of tissue damage, less neutrophil and macrophage infiltration, 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 inflammatory response resulting in mice death. Supplementary Information The online version contains supplementary material available at 10.1007/s00011-022-01641-8.

TheAchromobacterType 3 secretion system drives pyroptosis and immunopathology via independent activation of NLRC4 and NLRP3 inflammasomes

“…Moreover, proinflammatory lung tissue damage occurred in mice infected with wildtype but not in those infected with the T3SS-deficient mutant. These findings agree with a recent study showing that A. xylosoxidans induced acute lung inflammation in mice 50 , which is consistent with the idea that macrophages undergo pyroptosis, a highly proinflammatory event. T3SS-defective bacteria were less efficiently cleared than wildtype, suggesting the T3SS may have a role in alerting the immune system, ultimately leading to bacterial clearance.…”

Identification of Virulence Factors Involved in a Murine Model of Severe Achromobacter xylosoxidans Infection

“…More recently, the role of inflammation and inflammatory signaling during Ax-mediated pneumonia in mice was addressed using CD14-deficient mice. CD14-deficient mice were protected from Ax-induced death, which was unrelated to bacterial burden ( 22 ). In general, bacterial strains used in most in vitro and limited in vivo studies are characterized only as far as the type of patient (CF), the frequency of isolation (occasional/chronic), or the tissue from which the bacterium was isolated (non-CF patients).…”

O desbalanço de CD36 e CD14 está correlacionado com os níveis de acetilcolina, de mediadores lipídicos e com a gravidade em pacientes infectados com SARS-CoV-2

“…Nosso laboratório está empenhado, entre outras pesquisas, a melhor esclarecer os papeis destes correceptores da imunidade inata. Neste sentido, estudos de nosso grupo [100], [101], [165], [166] demonstram o importante entrelaçamento de CD14 e CD36 com as vias das respostas imunológicas envolvidas com a mediação lipídica, acetilcolina e citocinas. Sumariamente, um resumo didático é mostrado na Figura 6 sobre as funções de maiores relevâncias do CD36.…”