Innate Immune Effectors Play Essential Roles in Acute Respiratory Infection Caused by Klebsiella pneumoniae

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.

Vaccination induces rapid protection against bacterial pneumonia via training alveolar macrophage in mice

“…Clinical strains of A. baumannii SJZ24, SJZ26, and SJZ09 were isolated from Bethune International Peace Hospital in Shijiazhuang, China, in 2016 ( Zeng et al, 2019 ). P. aeruginosa strain XN-1 ( Gao et al, 2020 ), K. pneumoniae strain YBQ ( Liu et al, 2020 ), and S. pneumoniae were isolated from Chongqing Southwest Hospital. S. aureus strain KM-22 was isolated from the Second Affiliated Hospital of Kunming Medical University ( Zeng et al, 2020 ).…”

The Therapeutic Treatment with the GAG-Binding Chemokine Fragment CXCL9(74–103) Attenuates Neutrophilic Inflammation and Lung Dysfunction during Klebsiella pneumoniae Infection in Mice

“…The recruitment of neutrophils to the lungs during infection is essential for bacterial clearance and to avoid its dissemination. Indeed, depletion of neutrophils increases the bacterial burden in the lungs of mice infected with K. pneumoniae [ 7 , 8 ]. At the site of infection, activated neutrophils play a fundamental role in bacterial killing by a range of antimicrobial tools [ 9 ].…”

Genomic and Immunological Characterization of Hypermucoviscous Carbapenem-Resistant Klebsiella pneumoniae ST25 Isolates from Northwest Argentina

“…Furthermore, the work showed that CCR2 + monocytes were the main producers of TNF-α in infected mice. Work carried out in mice challenged with clinical isolates of K. pneumoniae also showed increases in the pulmonary levels of TNF-α, IL-1β, IL-6 [32], CXCL1, MCP-1, and MIP-2 [33], as well as neutrophil infiltration in the respiratory tract [32,33].…”

“…On the other hand, studies carried out in immunocompetent mice infected with the clinical isolates K. pneumoniae KPC+ or OXA-48+ showed that doses of 10 7 CFUs or higher are necessary to achieve a respiratory infection that reaches densities of 6-7 log 10 CFUs/g lung [31]. Similarly, doses of 10 8 CFUs were required to achieve respiratory infections in adult C57BL/6 [32] and BALB/c [33] mice with clinical isolates of K. pneumoniae. Consistent with these studies, doses of 10 7 CFUs or higher of LABACER 01 or LABACER 27 were required in this study to achieve respiratory infection in adult immunocompetent BALB/c mice.…”