Abstract
Innate immune effectors constitute the first line of host defense against pathogens. However, the roles of these effectors are not clearly defined during Klebsiella pneumoniae (K. pneumoniae) respiratory infection. In the current study, we established an acute pneumonia model of K. pneumoniae respiratory infection in mice and confirmed that the injury was most severe 48 h post infection. Flow cytometric assay demonstrated that alveolar macrophages were the predominant cells in BALF before infection, and neutrophils were quickly recruited after infection, and this was in consistent with the kinetics of chemokine expression. Further, we depleted neutrophils, macrophages, and complement pathways in vivo and challenged these mice with a sublethal dose of K. pneumonia, the result showed that 80%, 60%, and 40% of mice were died in these groups, respectively, while no deaths occurred in the control group. Besides, innate immune effector depleted mice showed higher bacterial burdens in lungs and blood, companied with more severe lung damage and increased levels of cytokine/chemokine expression. These results demonstrated that the innate immune effectors are critical in the early controlling of K. pneumoniae infection, and neutrophils are the most important. Thus, alternative strategies targeting these innate immune effectors may be effective in controlling of K. pneumoniae respiratory infection.
Highlights
Klebsiella pneumoniae (K. pneumoniae) is an opportunistic pathogen that frequently causes life-threatening infections, such as pneumonia, sepsis, and urinary tract infection, in healthy and immune compromised individuals [1]
The results showed that the number of total cells increased quickly after K. pneumoniae infection; a significant difference in the number of total cells was observed 4 h after infection as compared with 0 h, and it reached maximum at 24 h and decreased rapidly over time (Figure 3(a))
The results showed that the highest levels of all the three chemokines were observed in neutrophil depleted mice, which were 18-fold, 25-fold, and 12-fold higher as compared with that in control mice, this result again confirmed that neutrophils played an essential role in controlling of K. pneumoniae infection
Summary
Klebsiella pneumoniae (K. pneumoniae) is an opportunistic pathogen that frequently causes life-threatening infections, such as pneumonia, sepsis, and urinary tract infection, in healthy and immune compromised individuals [1]. It accounts for 5-20% of cases of Gram-negative sepsis [2, 3], resulting in significant mortality between 27.4% and 37% [4], and 48% of mortality was observed in patients in ICUs with K. pneumoniae infection [5]. Alveolar macrophages are resident mononuclear phagocytes that localize at the boundary between the lungs and external environment, which can recognize and eliminate pathogens before neutrophil recruitment in response to infection [18,19,20,21,22]. The complement system has the ability to kill invading pathogens by opsonophagocytosis
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