Induction of Functional Defects in Macrophages by a Poult Enteritis and Mortality Syndrome-Associated Turkey Astrovirus

Abstract

The interaction of a poult enteritis and mortality syndrome (PEMS)-turkey astrovirus-Ohio State University (TAst-OSU) with the mononuclear phagocytic system cells, namely macrophages, was examined after in vitro and in vivo exposure. In vitro exposures were performed by incubating adherent turkey macrophages with various volumes of 10(6) 50% embryo infective dose (EID50)/ml TAst-OSU stock, whereas for in vivo challenge, poults were given a 200 microl inoculum of 10(6) EID50/ml TAst-OSU stock at 7 days of age. Results show that TAst-OSU in vitro exposure reduced macrophage viability relative to controls (P < 0.05) and decreased phagocytosis (P < 0.05) and intracytoplasmic killing of Escherichia coli (P < 0.05) after a 42-48-hr exposure. Poults challenged with TAst-OSU in vivo recruited almost 50% fewer Sephadex-elicited inflammatory cells in the abdominal cavity (P < 0.05) as compared with the sham controls. Similar to in vitro exposure, macrophages isolated from in vivo TAst-OSU-challenged poults exhibited reduced percentage of phagocytic macrophages (P < 0.05) as well as fewer intracytoplasmic E. coli per phagocytic macrophage (P < 0.05). TAst-OSU-challenged poults had a greater number of viable E. coli in their spleens (P < 0.05) after an intravenous E. coli challenge as compared with the non-TAst-OSU-challenged control poults. Macrophage-mediated cytokines and metabolites were also examined during this study. Both in vitro and in vivo TAst-OSU challenge resulted in reduced interleukin (IL)-1 and IL-6 activity. On the contrary, nitrite levels in macrophage culture supernatant fraction of TAst-OSU-challenged macrophages were significantly higher (P < or = 0.05). The findings of these studies indicated that TAst-OSU challenge induced defects in macrophage effector functions, implying that PEMS-turkey astrovirus can potentially impair the immune response of turkeys, thereby leading to enhanced susceptibility of turkeys to secondary, perhaps even fatal, bacterial infections.

Human Astroviruses

“…In the context of TAstV infection, macrophages showed decreased phagocytosis and intracytoplasmic bacterial killing, and reduced activities of macrophagemediated proinflammatory cytokines (interleukin-1 [IL-1] and IL-6) were also detected, leading to an increase in the susceptibility of turkeys to secondary infections (140). Infection also compromised the lymphocyte-mediated immune defenses by reducing lymphoproliferative responses (141) and induced increased levels of active TGF-␤ in serum (122).…”

Immunity and Resistance to Astrovirus Infection

“…While these observations indicate NO was capable of modulating TAstV-2 replication, the cells in infected intestines responsible for producing NO have not been identified. Macrophages isolated from infected turkeys and stimulated ex vivo produced more NO than macrophages from control birds (20,39). These cells also demonstrated a reduced phagocytic function as compared with controls (39).…”

“…Macrophages isolated from infected turkeys and stimulated ex vivo produced more NO than macrophages from control birds (20,39). These cells also demonstrated a reduced phagocytic function as compared with controls (39). Analysis of the cytokines produced by these ex vivo stimulated cells indicated a reduction in IL-1 and IL-6 as compared to controls (39).…”

“…These cells also demonstrated a reduced phagocytic function as compared with controls (39). Analysis of the cytokines produced by these ex vivo stimulated cells indicated a reduction in IL-1 and IL-6 as compared to controls (39). IL-1 and IL-6 are both acute phase proteins involved in T-cell activation and B-cell differentiation (5).…”

“…The results from BAstV, OAstV, and TAstV-2 studies suggest that macrophages and the innate immune system are involved in the response to astrovirus infection (20,39,43,49). This is expected given the need for antigen presentation and co-stimulation of B-cells and T-cells to achieve a robust adaptive response.…”