Susceptibility to Aspergillus Infections in Rats with Chronic Obstructive Pulmonary Disease via Deficiency Function of Alveolar Macrophages and Impaired Activation of TLR2.
Clinical evidence indicates that patients with severe chronic obstructive pulmonary disease (COPD) are more susceptible to Aspergillus. However, the exact mechanisms underlying this effect are not known. In this study, we used cigarette smoke exposure to generate COPD rat model. colony-forming units (CFU) count assessment and phagocytosis were applied to evaluate the defense function of COPD rats against Aspergillus challenge. ELISA, western blotting, and GST-Rac1 pull-down assays were conducted to determine the expressions of cytokines and TLR2-associated signaling pathway. Our data showed that Aspergillus burdens increased, phagocytosis of Aspergillus as well as the expressions of inflammatory cytokines from alveolar macrophages (AMs) were impaired in COPD rats compared with normal rats. Though TLR2 signaling-related proteins were induced in response to the stimulation of Aspergillus or Pam3csk4 (TLR2 agonist), the activation of TLR2-associated signaling pathway was apparently interfered in rats with COPD, compared to that in normal rats. Taken together, our study demonstrated that COPD caused the deficiency of AMs function and impaired the activation of TLR2/PI3K/Rac 1 signaling pathway, leading to invasion of Aspergillus infection, which also provides a future basis for the infection control in COPD patients.
Graduate School, Southern Medical University, No1023, Shatai South Street, Guangzhou, Guangdong, 510515, China.
Yuting
Y
Wu
Respiratory Center of PLA, General Hospital of Guangzhou Command of PLA, Gangzhou, Guangdong, 510010, China.
Hong
H
Xu
Respiratory Center of PLA, General Hospital of Guangzhou Command of PLA, Gangzhou, Guangdong, 510010, China.
Li
L
Li
Respiratory Center of PLA, General Hospital of Guangzhou Command of PLA, Gangzhou, Guangdong, 510010, China.
Weifeng
W
Yuan
Department of elderly Respiratory, General Hospital of Guangzhou Command of PLA, Guangzhou, Guangdong, 510010, China.
Deming
D
Zhang
Graduate School, Southern Medical University, No1023, Shatai South Street, Guangzhou, Guangdong, 510515, China. huangyelu1029@vip163.com.|Respiratory Center of PLA, General Hospital of Guangzhou Command of PLA, Gangzhou, Guangdong, 510010, China. huangyelu1029@vip163.com.
Wenjie
W
Huang
D000818:Animals; D001228:Aspergillosis / Q000209:etiology*; D016207:Cytokines / Q000378:metabolism; D004198:Disease Susceptibility; D016676:Macrophages, Alveolar / Q000502:physiology*; D010587:Phagocytosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000503:physiopathology* / Q000821:virology; D051381:Rats; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
D016207:Cytokines; C495343:Tlr2 protein, rat; D051195:Toll-Like Receptor 2
Aspergillus; TLR2; alveolar macrophages; chronic obstructive pulmonary disease