Poster Session - Abstract # 15

Neuroimmune Regulation of Carbapenem-resistant Klebsiella pneumoniae Infection and Lethal Pneumonia

Prabhu R. Joshi, Pankaj Baral

Division of Biology, Kansas State University, Manhattan, KS, USA, 66506

Carbapenem-resistant Klebsiella pneumoniae (CRKP) causes lung infections and fatal pneumonia for which minimal treatment options are available.  They are responsible for 20-40% mortality among the hospitalized patients.  Host targeted alternative therapeutic approaches are thus necessary for CRKP infections.  The respiratory tract is densely innervated by nociceptive sensory neurons that mediate pain production and release of neuropeptide calcitonin gene-related peptide (CGRP) in the lungs.  CGRP acts on its cognate receptor complex (Ramp1/Calcrl) expressed in immune cells for immunomodulation.  However, we do not yet understand the role of nociceptive neurons and CGRP in host defenses to CRKP pneumonia.  Our preliminary data demonstrate the inhibitory effects of CGRP signaling for the immune responses to CRKP infections.  In vitro stimulation of bone marrow-derived macrophages (BMDMs) with CRKP bacteria of multiplicity of infection of 10 and 100nM CGRP showed a robust suppression of production of cytokines and chemokines that are essential for anti-CRKP immunity, including TNFa, MCP-1 and IFN-β.  In addition, our in vivo data after lethal dose challenge of CRKP showed a lower bacterial load in lungs and higher recruitment of neutrophils (CD11b⁺Ly6G⁺) and inflammatory monocytes (CD11b⁺Ly6C^hi) among nociceptive neuron-ablated mice as compared to control littermates.  Taken together, our results suggest the role of nociceptive neuronal signaling to immune cells in host response against CRKP infection.

Key words: Nociceptive neuron, CGRP, CRKP.