Length-Dependent Modulation of B Cell Activating Factor Transcripts in Chicken Macrophage by Viral Double-Stranded RNA

Abstract

Viral double-stranded RNA (dsRNA) interacts with Retinoic-acid-inducible-gene-1 (RIG-1)-like receptors (RLRs) to induce type 1 interferons. Melanoma-derived-antigen-5 (MDA-5), an RLR, but not RIG-1, is found in chickens. Ducks express both RIG-1 and MDA-5, a possible cause of differences in susceptibility to influenza virus infection between chickens and ducks. Using the HD11 chicken macrophage cell line and an RT2 Profiler PCR-array system, we showed that high-molecular-weight poly(I:C), HMW-poly(I:C), upregulates CCL4, interferon-gamma, interleukin-1, and interleukin-6 mRNA transcripts. HMW-poly(I:C), an in vitro surrogate of long dsRNA species, also induces the upregulation of IL-12B and B cell activating factor (BAFF). Conversely, low-molecular-weight poly(I:C), LMW-poly(I:C) did not induce a distinct cytokine expression pattern. Nonetheless, co-transfection of LMW and HMW-poly(I:C) significantly reduced the upregulation of IL12B and BAFF by HMW-poly(I:C). These findings support previous studies that found no expression of RIG-1, a receptor for short dsRNA species, in chicken cells. Surprisingly, however, our data suggested that in the absence of RIG-1 in chicken macrophages, short dsRNA species may inhibit macrophage-mediated B cell development and survival by modulating the expression of BAFF without significantly reducing type 1 interferon response.