AUTHOR=van der Geest Rick , Fan Hongye , Peñaloza Hernán F. , Bain William G. , Xiong Zeyu , Kohli Naina , Larson Emily , Sullivan Mara L. G. , Franks Jonathan M. , Stolz Donna B. , Ito Ryota , Chen Kong , Doi Yohei , Harriff Melanie J. , Lee Janet S. 

TITLE=Phagocytosis is a primary determinant of pulmonary clearance of clinical Klebsiella pneumoniae isolates

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1150658

DOI=10.3389/fcimb.2023.1150658

ISSN=2235-2988

ABSTRACT=<sec><title>Introduction</title><p><italic>Klebsiella pneumoniae</italic> (<italic>Kp</italic>) is a common cause of hospital-acquired pneumonia. Although previous studies have suggested that evasion of phagocytic uptake is a virulence determinant of <italic>Kp</italic>, few studies have examined phagocytosis sensitivity in clinical <italic>Kp</italic> isolates.</p></sec><sec><title>Methods</title><p>We screened 19 clinical respiratory <italic>Kp</italic> isolates that were previously assessed for mucoviscosity for their sensitivity to macrophage phagocytic uptake, and evaluated phagocytosis as a functional correlate of <italic>in vivo Kp</italic> pathogenicity.</p></sec><sec><title>Results</title><p>The respiratory <italic>Kp</italic> isolates displayed heterogeneity in the susceptibility to macrophage phagocytic uptake, with 14 out of 19 <italic>Kp</italic> isolates displaying relative phagocytosis-sensitivity compared to the reference <italic>Kp</italic> strain ATCC 43816, and 5 out of 19 <italic>Kp</italic> isolates displaying relative phagocytosis-resistance. Intratracheal infection with the non-mucoviscous phagocytosis-sensitive isolate S17 resulted in a significantly lower bacterial burden compared to infection with the mucoviscous phagocytosis-resistant isolate W42. In addition, infection with S17 was associated with a reduced inflammatory response, including reduced bronchoalveolar lavage fluid (BAL) polymorphonuclear (PMN) cell count, and reduced BAL TNF, IL-1β, and IL-12p40 levels. Importantly, host control of infection with the phagocytosis-sensitive S17 isolate was impaired in alveolar macrophage (AM)-depleted mice, whereas AM-depletion had no significant impact on host defense against infection with the phagocytosis-resistant W42 isolate.</p></sec><sec><title>Conclusion</title><p>Altogether, these findings show that phagocytosis is a primary determinant of pulmonary clearance of clinical <italic>Kp</italic> isolates.</p></sec>