Journal of Clinical & Experimental Pathology
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Klebsiella pneumoniae (KPn) is an important causative agent of nosocomial and community acquired pneumonia and
sepsis. Although innate immune mechanisms play an important role in development of sepsis, these are not well defined
in pathogenesis of KPn infection. The goal of this study was to elucidate the role of an innate immune C-type lectin receptor,
Clec4d in pulmonary infection of mice with this pathogen. As such, the function of this receptor in host immunity to any
infection is completely undefined. Here, we report that compared to the wild-type (WT) C57BL/6 mice, the Clec4d-/- mice
were highly susceptible to pulmonary infection with KPn and showed 100% mortality by day 4 of infection. This coincided with
a higher bacterial burden in lungs, liver and blood of these mice as compared to their WT counterparts. While lungs of WT as
well as Clec4d-/- mice showed infiltration of neutrophils early during infection, the WT mice showed resolution of this cellular
infiltration by day 3 p.i. whereas the Clec4d-/- mice showed increased neutrophil infiltration and severe tissue pathology at that
time p.i. in the lungs. This correlated with overwhelming levels of inflammatory cytokines in the knock-out mice reminiscent of
hypercytokinemia, a characteristic feature of sepsis. These results demonstrate that Clec4d-associated responses modulate the
disease severity and sepsis development during pulmonary infection with KPn. This is the first report of the role of Clec4d in a
pulmonary infection model.
Dr. Jyotika Sharma completed her Ph.D. in plant microbiology jointly from Jawaharlal Nehru University and Kanpur University, India. In August 2011, she joined the Department of Microbiology and Immunology at the University of North Dakota, as Assistant Professor. Major research focus of her laboratory is to elucidate the role of host derived factors called alarmins and the host C-type lectin receptors in the development of sepsis. She has published 16 papers in peer-reviewed journals and her research is currently funded by grants from American Heart Association and North Dakota EPSCor.
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