CXCL4 contributes to host defense against acute Pseudomonas aeruginosa lung infection

Lei Yue; Zheng Pang; Hua Li; Ting Yang; Lei Guo; Longding Liu; Junjie Mei; Xia Song; Tianhong Xie; Ye Zhang; Xin He; Tong-Jun Lin; Zhongping Xie

doi:10.1371/journal.pone.0205521

CXCL4 contributes to host defense against acute Pseudomonas aeruginosa lung infection

PLoS One. 2018 Oct 8;13(10):e0205521. doi: 10.1371/journal.pone.0205521. eCollection 2018.

Authors

Lei Yue¹, Zheng Pang², Hua Li¹, Ting Yang¹, Lei Guo¹, Longding Liu¹, Junjie Mei¹, Xia Song¹, Tianhong Xie¹, Ye Zhang¹, Xin He¹, Tong-Jun Lin^{1

2

3

4

5}, Zhongping Xie¹

Affiliations

¹ The Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan, China.
² Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
³ Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
⁴ Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
⁵ Beatrice Hunter Cancer Research Institute, Halifax, Nova Scotia, Canada.

Abstract

Platelets have been implicated in pulmonary inflammation following exposure to bacterial stimuli. The mechanisms involved in the platelet-mediated host response to respiratory bacterial infection remain incompletely understood. In this study, we demonstrate that platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) plays critical roles in a mouse model of acute bacterial pneumonia using Pseudomonas aeruginosa. Platelets are activated during P. aeruginosa infection, and mice depleted of platelets display markedly increased mortality and impaired bacterial clearance. CXCL4 deficiency impairs bacterial clearance and lung epithelial permeability, which correlate with decreased neutrophil recruitment to BALF. Interestingly, CXCL4 deficiency selectively regulates chemokine production, suggesting that CXCL4 has an impact on other chemokine expression. In addition, CXCL4 deficiency reduces platelet-neutrophil interactions in blood following P. aeruginosa infection. Further studies revealed that platelet-derived CXCL4 contributes to the P. aeruginosa-killing of neutrophils. Altogether, these findings demonstrate that CXCL4 is a vital chemokine that plays critical roles in bacterial clearance during P. aeruginosa infection through recruiting neutrophils to the lungs and intracellular bacterial killing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blood Platelets / immunology
Bronchoalveolar Lavage Fluid / immunology
Bronchoalveolar Lavage Fluid / microbiology
Disease Models, Animal
Epithelial Cells / immunology
Epithelial Cells / microbiology
Gene Expression Regulation
Host Microbial Interactions / immunology*
Lung / immunology
Lung / microbiology
Mice, Inbred C57BL
Mice, Knockout
Neutrophils / immunology
Platelet Factor 4 / genetics
Platelet Factor 4 / metabolism*
Pneumonia, Bacterial / blood
Pneumonia, Bacterial / immunology*
Pneumonia, Bacterial / mortality
Pseudomonas Infections / blood
Pseudomonas Infections / immunology*
Pseudomonas Infections / mortality
Pseudomonas aeruginosa*

Substances

Platelet Factor 4

Grants and funding

TJL has received grant support from the National Natural Science Foundation of China (81471564) (http://www.nsfc.gov.cn). LY is supported by Yunnan Natural Science Foundation (2016FB037, 2017FB019) (http://www.ynstc.gov.cn), PUMC Youth Fund (3332016114) (http://www.cams.ac.cn), Fundamental Research Funds for the Central Universities (2016ZX350070) (http://www.cams.ac.cn) and CAMS Innovation Fund for Medical Sciences (2017-I2M-2-006) (http://www.cams.ac.cn). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.