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

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..

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:71

Enthalten in:

Inflammation research - 71(2022), 12 vom: 25. Okt., Seite 1535-1546

Sprache:

Englisch

Beteiligte Personen:

Elias-Oliveira, Jefferson [VerfasserIn]
Prado, Morgana Kelly Borges [VerfasserIn]
Souza, Camila Oliveira Silva [VerfasserIn]
Pastore, Marcella Roverato [VerfasserIn]
Ramos, Simone Gusmão [VerfasserIn]
Costa Darini, Ana Lúcia [VerfasserIn]
Gardinassi, Luiz Gustavo [VerfasserIn]
Faccioli, Lúcia Helena [VerfasserIn]

Links:

Volltext [lizenzpflichtig]

Themen:

CD14
Pneumonia
Soluble CD14

Anmerkungen:

© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

doi:

10.1007/s00011-022-01641-8

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC2132705364