TY - JOUR
T1 - The Protective Role of Interleukin 17A in Acinetobacter baumannii Pneumonia Is Associated with Candida albicans in the Airway
AU - Tang, Jiaxin
AU - Li, Jiamin
AU - Pan, Jinqing
AU - Shen, Xiaoyuan
AU - Ye, Xiangsheng
AU - Zhou, Jiamin
AU - Wang, Ni
AU - Xie, Liang
AU - Fuchs, Beth Burgwyn
AU - Lionakis, Michail S.
AU - Mylonakis, Eleftherios
AU - Tan, Xiaojiang
N1 - Funding Information:
This work was supported in part by the Division of Intramural Research of the NIAID/ NIH (ZIA AI001175 to M.S.L.). This work was supported by the National Natural Science Foundation of China (grant 81570012) to X.T. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We have no financial disclosures.
Publisher Copyright:
Copyright © 2023 American Society for Microbiology. All Rights Reserved.
PY - 2023/1/24
Y1 - 2023/1/24
N2 - Recent studies have found that the coexistence of fungi and bacteria in the airway may increase the risk of infection, contribute to the development of pneumonia, and increase the severity of disease. Interleukin 17A (IL-17A) plays important roles in host resistance to bacterial and fungal infections. The objective of this study was to determine the effects of IL-17A on Acinetobacter baumannii-infected rats with a previous Candida albicans airway inoculation. The incidence of A. baumannii pneumonia was higher in rats with C. albicans in the airway than in noninoculated rats, and it decreased when amphotericin B was used to clear C. albicans, which influenced IL-17A levels. IL-17A had a protective effect in A. baumannii pneumonia associated with C. albicans in the airway. Compared with A. baumannii-infected rats with C. albicans in the airway that did not receive IL-17A, recombinant IL-17A (rIL-17A) supplementation decreased the incidence of A. baumannii pneumonia (10/15 versus 5/17;
P = 0.013) and the proportion of neutrophils in the lung (84 ± 3.5 versus 74 ± 4.3%;
P = 0.033), reduced tissue destruction and inflammation, and decreased levels of myeloperoxidase (MPO) (1.267 ± 0.15 versus 0.233 ± 0.06 U/g;
P = 0.0004), reactive oxygen species (ROS) (132,333 ± 7,505 versus 64,667 ± 10,115 AU;
P = 0.0007) and lactate dehydrogenase (LDH) (2.736 ± 0.05 versus 2.1816 ± 0.29 U/g;
P = 0.0313).
In vitro experiments revealed that IL-17A had no significant effect on the direct migration ability and bactericidal capability of neutrophils. However, IL-17A restrained lysis cell death and increased apoptosis of neutrophils (2.9 ± 1.14 versus 7 ± 0.5%;
P = 0.0048). Taken together, our results suggest that C. albicans can depress IL-17A levels, which when supplemented may have a regulatory function that limits the accumulation of neutrophils in inflammatory areas, providing inflammatory response homeostasis.
AB - Recent studies have found that the coexistence of fungi and bacteria in the airway may increase the risk of infection, contribute to the development of pneumonia, and increase the severity of disease. Interleukin 17A (IL-17A) plays important roles in host resistance to bacterial and fungal infections. The objective of this study was to determine the effects of IL-17A on Acinetobacter baumannii-infected rats with a previous Candida albicans airway inoculation. The incidence of A. baumannii pneumonia was higher in rats with C. albicans in the airway than in noninoculated rats, and it decreased when amphotericin B was used to clear C. albicans, which influenced IL-17A levels. IL-17A had a protective effect in A. baumannii pneumonia associated with C. albicans in the airway. Compared with A. baumannii-infected rats with C. albicans in the airway that did not receive IL-17A, recombinant IL-17A (rIL-17A) supplementation decreased the incidence of A. baumannii pneumonia (10/15 versus 5/17;
P = 0.013) and the proportion of neutrophils in the lung (84 ± 3.5 versus 74 ± 4.3%;
P = 0.033), reduced tissue destruction and inflammation, and decreased levels of myeloperoxidase (MPO) (1.267 ± 0.15 versus 0.233 ± 0.06 U/g;
P = 0.0004), reactive oxygen species (ROS) (132,333 ± 7,505 versus 64,667 ± 10,115 AU;
P = 0.0007) and lactate dehydrogenase (LDH) (2.736 ± 0.05 versus 2.1816 ± 0.29 U/g;
P = 0.0313).
In vitro experiments revealed that IL-17A had no significant effect on the direct migration ability and bactericidal capability of neutrophils. However, IL-17A restrained lysis cell death and increased apoptosis of neutrophils (2.9 ± 1.14 versus 7 ± 0.5%;
P = 0.0048). Taken together, our results suggest that C. albicans can depress IL-17A levels, which when supplemented may have a regulatory function that limits the accumulation of neutrophils in inflammatory areas, providing inflammatory response homeostasis.
KW - Acinetobacter baumannii
KW - Candida albicans
KW - apoptosis
KW - interleukin 17A
KW - neutrophils
KW - Candida albicans/metabolism
KW - Lung/metabolism
KW - Pneumonia
KW - Neutrophils/metabolism
KW - Acinetobacter Infections
KW - Rats
KW - Interleukin-17/metabolism
KW - Pneumonia, Bacterial
KW - Bacteria/metabolism
KW - Animals
KW - Acinetobacter baumannii/metabolism
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U2 - 10.1128/iai.00378-22
DO - 10.1128/iai.00378-22
M3 - Article
C2 - 36602381
AN - SCOPUS:85147048260
SN - 0019-9567
VL - 91
SP - e0037822
JO - Infection and Immunity
JF - Infection and Immunity
IS - 1
ER -