title: C-type lectin receptor Clec4d plays a protective role in resolution of Gram-negative pneumonia.
abstract: Pneumonia is frequently associated with sepsis, characterized by a nonresolving hyperinflammation. However, specific host components of the pulmonary milieu that regulate the perpetuation of inflammation and tissue destruction observed in this immune disorder are not clearly understood. We examined the function of Clec4d, an orphan mammalian CLR, in Gram negative pneumonic sepsis caused by KPn. Whereas the WT mice infected with a sublethal dose of bacteria could resolve the infection, the Clec4d(-/-) mice were highly susceptible with a progressive increase in bacterial burden, hyperinflammatory response typical of sepsis, and severe lung pathology. This correlated with a massive accumulation of neutrophils in lungs of infected Clec4d(-/-) mice, which was in contrast with their WT counterparts, where neutrophils transiently infiltrated the lungs. Interestingly, the Clec4d(-/-) neutrophils did not exhibit any defect in bacterial clearance. These results suggest that Clec4d plays an important role in resolution of inflammation, possibly by facilitating neutrophil turnover in lungs. This is the first report depicting the physiological function of Clec4d in a pathological condition. The results can have implications not only in sepsis but also in other inflammatory diseases, where nonresolving inflammation is the root cause of disease development.
authors.affiliation: Department of Microbiology and Immunology, The University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota 58202-9037, USA.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Steichen
authors.forename: Brandilyn J
authors.initials: BJ
authors.lastname: Binstock
authors.forename: Bibhuti B
authors.initials: BB
authors.lastname: Mishra
authors.forename: Jyotika
authors.initials: J
authors.lastname: Sharma
mesh_terms: D000818:Animals; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000276:immunology*; D037181:Lectins, C-Type / Q000502:physiology*; D008168:Lung / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000276:immunology*; D011971:Receptors, Immunologic / Q000502:physiology*
chemical_list: C584161:Clec4d protein, mouse; D037181:Lectins, C-Type; D011971:Receptors, Immunologic
keywords: Clecsf8; Klebsiella pneumoniae; efferocytosis; hyperinflammation; sepsis