Tolerance and Cross-Tolerance following Toll-Like Receptor (TLR)-4 and -9 Activation Are Mediated by IRAK-M and Modulated by IL-7 in Murine Splenocytes.

ABSTRACT:

Objective

Immune suppression during critical illness predisposes to serious infections. We sought to determine the mechanisms regulating tolerance and cross-tolerance to common pro-inflammatory danger signals in a model that recapitulates the intact in vivo immune response.

Materials and methods

Flt3-expanded splenocytes obtained from wild-type or matching IRAK-M knockout (IRAK-M-/-), C57BL/6, male mice (8-10 weeks old) were treated repeatedly or alternately with either LPS or CpGA DNA, agonists of Toll-like receptor (TLR)-4 and -9, respectively, over successive 24-hour periods. Supernatants were collected following each 24-hour period with cytokine release (ELISA) and splenocyte IRAK-M expression (Western blot) determined. Tolerance and cross-tolerance were assessed in the

SUBMITTER: Julian MW 

PROVIDER: S-EPMC4517781 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature