Dramatic differences in the response of macrophages from B2 and B19 MHC-defined haplotypes to interferon gamma and polyinosinic:polycytidylic acid stimulation

Abstract

The chicken MHC has been associated with disease resistance, though the mechanisms are not understood. The functions of macrophages, critical to both innate and acquired immunity, were compared between the more infectious bronchitis virus-resistant B2 and the more infectious bronchitis virus-susceptible B19 lines. In vivo peripheral blood concentrations of monocytes were similar in B2 or B19 homozygous haplotypes. Peripheral blood-derived macrophages were stimulated with poly I:C, simulating an RNA virus, or IFNγ, a cytokine at the interface of innate and adaptive immunity. Not only did B2-derived peripheral monocytes differentiate into macrophages more readily than the B19 monocytes, but as determined by NO production, macrophages from B2 and B2 on B19 genetic background chicks were also significantly more responsive to either stimulant. In conclusion, the correlation with resistance to illness following viral infection may be directly linked to a more vigorous innate immune response.

Establishment of six homozygous MHC-B haplotype populations associated with susceptibility to Marek’s disease in Chinese specific pathogen-free BWEL chickens

“…Therefore, selective breeding, based in part on viral clinical signs, has led to the development of chicken lines with resistant or susceptible phenotypes. Genetic resistance or susceptibility to MD may be mediated by differential host responses to the virus, e.g., the cytotoxic response to viral antigens (Garcia-Camacho et al, 2003), the cytotoxic T-lymphocyte response (Omar and Schat, 1997), innate immunity (Dawes et al, 2014) and changes in host gene expression (Kaiser et al, 2003;Sarson et al, 2008). In order to benefit in clarifying the molecular mechanisms responsible for host immune responses, it is very essential to establish MHC-B haplotype chicken populations in China.…”

“…For example, B21 chickens are highly resistant to MD while B19 chickens are highly susceptible. The severity of infection may thus depend partly on the genetic background of the infected chickens, including differences in immune responses (Dawes et al, 2014;Garcia-Camacho et al, 2003;Kaiser et al, 2003;Omar and Schat, 1997;Sarson et al, 2008). Furthermore, MHC-B haplotypes also played a very important role in vaccinal immunity against MD in both experimental and commercial chicken strains (Chang et al, 2010).…”

RNA sequencing demonstrates large-scale temporal dysregulation of gene expression in stimulated macrophages derived from MHC-defined chicken haplotypes

“…B2 haplotype chickens are more resistant to avian coronavirus infection than B19 haplotypes and these differences in disease resistance were observed early after infection in our previous studies [10]. This suggests that innate immunity plays a major role with the macrophage being a key player in this enhanced immune response as evidenced by the B2 haplotype birds' greater capability to produce nitric oxide (NO) in response to IFNγ and Poly I:C [13]. In addition, B2 macrophages activated T cells more efficiently than macrophages derived from B19 haplotypes [14].…”

“…Animal protocols were performed under the approval of the Institutional Animal Care and Use Committee at Western University of Health Sciences, Pomona, California (WesternU). Fertilized eggs, descended from Modified Wisconsin Line 3, were obtained from Dr. W. Elwood Briles, Northern Illinois University, and incubated and hatched under standard conditions at (38˚C/50-65% humidity) [10,13] at WesternU. In addition to daily health monitoring, fresh food and water were provided ad libitum.…”

“…These findings indicate that chickens with enhanced IFNγ production are more resistant to certain infections. IFNγ enhances macrophage activation, expression of MHC and nitric oxide release which aides in killing of pathogens and also increases activity of cytotoxic T cells and secretion of Th1 cytokines [31,13], underscoring how crucial this process is for innate immune competence.…”