Activation of Porcine Alveolar Macrophages by Actinobacillus pleuropneumoniae Lipopolysaccharide via the Toll-Like Receptor 4/NF-κB-Mediated Pathway

Abstract

is the causative agent of porcine contagious pleuropneumonia. Overproduction of proinflammatory cytokines, like interleukin-1β (IL-1β), IL-6, tumor necrosis factor alpha, and resistin, in the lung is an important feature of infection. These proinflammatory cytokines enhance inflammatory and immunological responses. However, the mechanism that leads to cytokine production remains unclear. As a major virulence factor of, lipopolysaccharide (LPS) may act as a potent stimulator of Toll-like receptor 4 (TLR4), triggering a number of intracellular signaling pathways that lead to the synthesis of proinflammatory cytokines. Porcine alveolar macrophages (PAMs) are the first line of defense against pathogenic microbes during pathogen invasion. The results of the present study demonstrate that LPS induces PAMs to produce inflammatory cytokines in time- and dose-dependent manners. Moreover, PAMs were activated by LPS, resulting in upregulation of signaling molecules, including TLR4, MyD88, TRIF-related adaptor molecule, and NF-κB. In contrast, the activation effects of LPS on PAMs could be suppressed by specific inhibitors, like small interfering RNA and Bay11-7082. Taken together, our data indicate that LPS can induce PAMs to produce proinflammatory cytokines via the TLR4/NF-κB-mediated pathway. These findings partially reveal the mechanism of the overproduction of proinflammatory cytokines in the lungs of swine with infection and may provide targets for the prevention of-induced pneumonia. All the data could be used as a reference for the pathogenesis of respiratory infection.

Effective Pro-Inflammatory Induced Activity of GALT, a Conserved Antigen in A. Pleuropneumoniae, Improves the Cytokines Secretion of Macrophage via p38, ERK1/2 and JNK MAPKs Signal Pathway

“…Bacterial death induces endotoxin release into circulation, often resulting in endotoxemia. In this stage of bacterial infection, pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 are elevated (Choi et al, 1999 ; Cho and Chae, 2002 ), playing a crucial role in the pathogenesis of acute bacterial infection (Li et al, 2018 ). In this study, secretion of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 from macrophages were significantly (P < 0.01) promoted after stimulation with GALT (Figure 3 ).…”

Resistin, a Novel Host Defense Peptide of Innate Immunity

“…It has been demonstrated that proinflammatory mediators such as LPS, tumor necrosis factor-alpha (TNF-a), interleukin 1b (IL-1b), and IL-6 can strongly induce the expression of resistin in monocytes/macrophages (12,(46)(47)(48). For instance, Actinobacillus pleuropneumoniae-LPS induces porcine alveolar macrophages to produce resistin via MyD88, TRAM, and NF-kB by interacting with TLR4 (49). Besides, the mRNA expression of resistin is also significantly upregulated in human peripheral blood-derived monocytes following exposure to microfilariae or antigen of Brugia malayi (50,51).…”

Transcriptome Analysis of Selenium-Treated Porcine Alveolar Macrophages Against Lipopolysaccharide Infection

“…Once infection occurs, AMs move between alveoli to sense and phagocytose inhaled bacteria before they can induce harmful lung inflammation (Neupane et al, 2020 ). Meanwhile, the Gram-negative bacterial LPS binding to the TLR4 of AMs initiates multiple intracellular signaling pathways and induces the production of some pro-inflammatory cytokines, such as interleukin 1β (IL-1β) (Li et al, 2017 ). These pro-inflammatory cytokines induce superfluous neutrophil recruitment, leading to continuous lung inflammation and injury.…”