TY - JOUR
T1 - C-type lectin receptor Clec4d plays a protective role in resolution of Gram-negative pneumonia
AU - Steichen, Anthony L.
AU - Binstock, Brandilyn J.
AU - Mishra, Bibhuti B.
AU - Sharma, Jyotika
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/9/1
Y1 - 2013/9/1
N2 - 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.
AB - 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.
KW - Clecsf8
KW - Efferocytosis
KW - Hyperinflammation
KW - Klebsiella pneumoniae
KW - Sepsis
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U2 - 10.1189/jlb.1212622
DO - 10.1189/jlb.1212622
M3 - Article
C2 - 23709686
AN - SCOPUS:84883219371
SN - 0741-5400
VL - 94
SP - 393
EP - 398
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 3
ER -