MyD88-Mediated Innate Immune Response in a Single Cat Dander Extract Challenge
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
John P. Kelley, MD, Koa Hosoki, MD, PhD, Sanjiv Sur, MD
Rationale: Increasing evidence is showing that innate immune responses, such as TLR2 and TLR4 signaling, contribute to the initiation of airway allergic disorders.  The shared adaptor for TLR2 and TLR4 is MyD88, but its role in initiation of allergic inflammation has not been reported. The objective of this study was to elucidate the contribution of MyD88 to cat dander induced innate mRNA expression in the lungs.

Methods: Cat Dander Extract (CDE) was administered intranasally to both wild type (WT) and MyD88 knock out (KO) mice in single dose challenges.  After exposure to CDE, the lung mRNA expression of 192 innate and allergic inflammation associated genes were quantified by qPCR arrays.

Results: A single CDE challenge in WT mice significantly increased lung mRNA expression of Ifnar1, C5ar1, Ccr8, Nfkb1, Cd4, Ifnb1, Cd80, Il17a, Il1b, Tlr2, Nlrp3, Icam1, Nfkbia, Il10, Ccl12, Nod2, Il1a, Il6, Csf2, Cxcl10, Tnf, and Il23a. Deletion of MyD88 significantly inhibited CDE-induced upregulation of the lung mRNA expression of Ccr8, Cd80, Csf2, Cxcl10, Icam1, Il17a, Il1b, Il23a, Il6, Nfkb1, Nfkb1a, Nlrp3, Nod2, Tlr2, and Tnf.

Conclusions: Panther analysis of CDE-induced genes suggest activation of the following signaling pathways: angiogenesis, apoptosis, B cell activation, CCKR, EGFR, chemokines, cytokines, Ras, T cell activation, TLR, VEGF, and Wnt. MyD88-mediates CDE-induced innate immune response consisting of 15 genes. The contribution of these genes and signaling pathways to CDE-induced allergic sensitization and inflammation needs to be elucidated in future studies.