Age-enhanced endoplasmic reticulum stress contributes to increased Atg9A inhibition of STING-mediated IFN-β production during Streptococcus pneumoniae infection.

Pneumococcal infections remain a leading cause of death in persons ≥ 65 y of age. Recent reports have illustrated detrimental changes in the endoplasmic reticulum stress response or unfolded protein response in aging and age-related diseases; however, the relationship between aging, the unfolded protein response, and innate immune responses to Streptococcus pneumoniae has not been fully elucidated. Our results illustrate that stimulator of IFN genes-mediated production of IFN-β during S.

Identification of residues of SARS-CoV nsp1 that differentially affect inhibition of gene expression and antiviral signaling.

An epidemic of Severe Acute Respiratory Syndrome (SARS) led to the identification of an associated coronavirus, SARS-CoV. This virus evades the host innate immune response in part through the expression of its non-structural protein (nsp) 1, which inhibits both host gene expression and virus- and interferon (IFN)-dependent signaling. Thus, nsp1 is a promising target for drugs, as inhibition of nsp1 would make SARS-CoV more susceptible to the host antiviral defenses.

Dynamics of the avian inflammatory response to Salmonella following administration of the Toll-like receptor 5 agonist flagellin.

Previous work has shown that flagellin (FGN) is a potent stimulator in vitro of phagocytic cell functions of chickens. The purpose of this study was to define the effects of FGN on the inflammatory response to Salmonella enteritidis (SE) in chickens. Intra-abdominal (IA) FGN administration caused significant increases in peripheral blood leukocytes (PBL) compared with SE-injected controls at 4 and 8 h postinjection (P View Article and Find Full Text PDF

Comparison of MAP and tyrosine kinase signaling in heterophils from commercial and wild-type turkeys.

Protein tyrosine and mitogen-activated kinases are crucial mediators of the host innate immune response, conferring signals from surface receptors on the host cell to the nucleus of the cell where gene expression occurs. Heterophils were isolated from wild-type Rio Grande turkeys and a commercial line of turkeys (Line A) on days 4 and 7 post-hatch. Heterophils were stimulated for 1h with Salmonella enteritidis (SE) or opsonized SE (OPSE).

Response of nitric oxide production to CpG oligodeoxynucleotides in turkey and chicken peripheral blood monocytes.

We evaluated the innate immune response to various synthetic CpG-containing oligodeoxynucleotides (CpG ODNs) by measuring nitric oxide production in the peripheral blood monocytes from turkey poults. The results indicate that the presence of the CpG dinucleotide in ODNs was a prerequisite for activation of turkey monocytes and induction of nitric oxide (NO) synthesis. CpG motifs and sequence structure of the ODNs were also found to influence stimulatory activity greatly.

Comparison of heterophil functions of modern commercial and wild-type Rio Grande turkeys.

The purpose of the present study was to measure any functional differences in peripheral blood heterophils isolated from a commercial turkey line to wild-type Rio Grande turkeys. The phagocytosis of Salmonella enteritidis, oxidative burst (OXB) and degranulation (DGR) were used as parameters of heterophil functional efficiency in these studies. Blood was collected and heterophils isolated from each line of turkeys at days 4, 7, and 14 post-hatch.

In vitro activation of chicken leukocytes and in vivo protection against Salmonella enteritidis organ invasion and peritoneal S. enteritidis infection-induced mortality in neonatal chickens by immunostimulatory CpG oligodeoxynucleotide.

Unmethylated CpG oligodinucleotides (CpG-ODN) flanked by specific bases found in bacterial DNA are known to stimulate innate immune responses. In this study, synthetic CpG-ODNs were evaluated for their in vitro stimulation of leukocyte and in vivo protection against Salmonella enteritidis (SE) in neonatal chickens. Our studies showed that CpG-ODN stimulated bactericidal activities, releasing granules (degranulation) and generating reactive oxygen species (oxidative burst), in chicken heterophils and up regulated nitric oxide production in chicken peripheral blood monocytes.

CpG-oligodeoxynucleotide-stimulated chicken heterophil degranulation is serum cofactor and cell surface receptor dependent.

Synthetic oligodeoxynucleotide containing unmethylated CpG motif (CpG-ODN) is immune stimulatory to chicken heterophils. Recognition of CpG-ODN by chicken heterophils leads to the mobilization and release of granules. This CpG-ODN-induced heterophil degranulation was chicken serum (CS)-dependent.

The use of selective pharmacological inhibitors to delineate signal transduction pathways activated during complement receptor-mediated degranulation in chicken heterophils.

Complement receptors (CRs), along with Fc receptors, play a primary role in the removal of bacterial pathogens in poultry. The binding of serum-opsonized bacteria to CR results in the secretion of both toxic oxygen metabolites and antibacterial granules. We have previously shown that the stimulation of chicken heterophils with serum-opsonized Salmonella enteritidis induced tyrosine kinase-dependent phosphorylation regulated degranulation.

rP33 activates bacterial killing by chicken peripheral blood heterophils.

The protection of poultry from infection by Salmonella is of major concern with regard to human health because Salmonella is a common bacterial cause of foodborne diseases, and protection without the use of antibiotics is preferable in order to avoid possible complications involving antibiotic resistance. Salmonella immune lymphokine (SILK), produced by stimulated splenic T cells from Salmonella Enteritidis-immunized chickens, has been shown to confer protection against Salmonella infection on day-old chicks without the use of antibiotics. This protection results from the potentiation of an immune response following treatment with SILK.

Functional comparison of heterophils isolated from commercial broiler chickens.

Heterophils from two pure lines (A and B) of commercial broiler chickens were isolated on days 1, 4, and 7 post-hatch to evaluate their ability to (1) phagocytose Salmonella enteritidis (SE) (2) degranulate when exposed to immune-IgG opsonized SE, and (3) produce an oxidative burst. On days 1 and 4, heterophils from line A were functionally more efficient compared to heterophils from line B (p<0.05).

Differential nitric oxide production by chicken immune cells.

Nitric oxide is a rapidly reacting free radical which has cytotoxic effects during inflammatory responses and regulatory effects as a component of signal transduction cascades. We quantified the production of nitrite, a stable metabolite of nitric oxide, in chicken heterophils, monocytes and macrophages after stimulation by IFNgamma, LPS and killed bacteria. Our results demonstrate a differential production of nitrite over 72 h by chicken peripheral blood heterophils, monocytes and the chicken macrophage cell line (HD11).

Selective pharmacological inhibitors reveal the role of Syk tyrosine kinase, phospholipase C, phosphatidylinositol-3'-kinase, and p38 mitogen-activated protein kinase in Fc receptor-mediated signaling of chicken heterophil degranulation.

Fc receptors of avian heterophils play a primary role in the elimination of bacterial pathogens in poultry. The cross-linking of Fc receptors with IgG-bacteria complexes results in the secretion of toxic oxygen metabolites and anti-bacterial granules. We have been investigating the upstream signaling events that precede degranulation following crosslinkage of Fc receptors on heterophils.