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Pete Kaiser

Publications and source records attributed to Pete Kaiser.

41 records · Page 3Linked to original sources

A role for IL-15 in driving the onset of spontaneous autoimmune thyroiditis?

The obese strain (OS) of chickens, which suffers from spontaneous autoimmune thyroiditis, is an excellent animal model for Hashimoto's thyroiditis and provides a unique opportunity to investigate the mechanisms underlying and driving the onset of the disease. Following recent advances in cloning chicken cytokines, we can now begin to investigate the role of cytokines in driving the lymphoid infiltration of the thyroid seen in these birds from day 7 posthatch. Using real-time quantitative RT-PCR, we characterized the expression of IFN-gamma, IL-1beta, IL-2, IL-6, IL-8, IL-15, and IL-18 in thyroids from OS birds and control CB line birds, both in the embryo just before hatch (embryonic day 20) and at 3 and 5 days posthatch. All of these cytokines were up-regulated compared with levels in thyroids from CB birds, at least at some time points, with some evidence for coordination of regulation, e.g., for the proinflammatory cytokines IL-1beta and IL-8. Only IL-15 was up-regulated at all time points. IL-15 was also shown to be up-regulated in spleens of OS birds at embryonic day 20 and 5 days posthatch, suggesting that IL-15 is constitutively up-regulated in this line of birds. This could explain the general immune system hyperreactivity exhibited by OS chickens and may be a factor driving the lymphoid infiltration of the thyroid.

Animals↗

Turkey and chicken interleukin-18 (IL18) share high sequence identity, but have different polyadenylation sites in their 3' UTR.

The cDNA of turkey interleukin-18 (IL18) was cloned, initially using oligonucleotide primers based on the sequence of the chicken IL18 gene. The coding regions of the turkey and chicken IL18 genes are highly conserved (96.1% nucleotide identical and 97.4% amino acid identical). The 3' UTR of the turkey IL18 mRNA contains two 'instability' motifs and a canonical polyadenylation site, as compared to the chicken IL18 mRNA which contains only one instability motif and lacks a canonical polyadenylation site. Phylogenetic analysis shows that turkey and chicken IL18 have diverged to a less extent than IL18 from closely related mammalian species. We predict that turkey and chicken IL18 will cross-react in functional assays.

3' Untranslated Regions↗

Differential effects of age on chicken heterophil functional activation by recombinant chicken interleukin-2.

Interleukin-2 (IL-2) exercises an array of biological effects on many cells including the functional activation of cells of the innate immune response. Heterophils, the avian equivalent of the neutrophil, function as professional phagocytes to aid in regulation of innate host defenses. The objective of the present studies was to examine the effects of recombinant chicken IL-2 (rChIL-2) on functional activities of heterophils from chickens during the first 3 weeks after hatch. Peripheral blood heterophils were isolated and incubated with either COS cell-derived rChIL-2 or supernatants from mock-transfected COS cells. rChIL-2 had no effect on the functional activities of heterophils from day-of-hatch chickens, but significantly increased the phagocytosis and bactericidal activity of heterophils from 7- and 14-day-old chickens. rChIL-2 induced no direct stimulation of the respiratory burst by heterophils, but primed heterophils from 7- and 14-day-old birds for an enhanced respiratory burst in response to phorbol ester stimulation. Lastly, rChIL-2 had neither direct nor priming effects on heterophil degranulation. The enhancing effects on heterophil functional activity by rChIL-2 were abated by a neutralizing anti-chicken IL-2 mAb and were therefore specific for this cytokine. These results show that rChIL-2 can directly activate chicken heterophils to exert effector functions, and that heterophil activation by rChIL-2 is also an age-dependent event.

Age Factors↗

Differential cytokine expression in avian cells in response to invasion by Salmonella typhimurium, Salmonella enteritidis and Salmonella gallinarum.

Salmonella enterica is a facultative intracellular pathogen that is capable of causing disease in a range of hosts. Although human salmonellosis is frequently associated with consumption of contaminated poultry and eggs, and the serotypes Salmonella gallinarum and Salmonella pullorum are important world-wide pathogens of poultry, little is understood of the mechanisms of pathogenesis of Salmonella in the chicken. Type III secretion systems play a key role in host cell invasiveness and trigger the production of pro-inflammatory cytokines during invasion of mammalian hosts. This results in a polymorphonuclear cell influx that contributes to the resulting enteritis. In this study, a chicken primary cell culture model was used to investigate the cytokine responses to entry by the broad host range serotypes S. enteritidis and S. typhimurium, and the host specific serotype S. gallinarum, which rarely causes disease outside its main host, the chicken. The cytokines interleukin (IL)-1ss, IL-2, IL-6 and interferon (IFN)-gamma were measured by quantitative RT-PCR, and production of IL-6 and IFN-gamma was also determined through bioassays. All serotypes were invasive and had little effect on the production of IFN-gamma compared with non-infected cells; S. enteritidis invasion caused a slight down-regulation of IL-2 production. For IL-1ss production, infection with S. typhimurium had little effect, whilst infection with S. gallinarum or S. enteritidis caused a reduction in IL-1ss mRNA levels. Invasion of S. typhimurium and S. enteritidis caused an eight- to tenfold increase in production of the pro-inflammatory cytokine IL-6, whilst invasion by S. gallinarum caused no increase. These findings correlate with the pathogenesis of Salmonella in poultry. S. typhimurium and S. enteritidis invasion produces a strong inflammatory response, that may limit the spread of Salmonella largely to the gut, whilst S. gallinarum does not induce an inflammatory response and may not be limited by the immune system, leading to the severe systemic disease fowl typhoid.

Animals↗

Early in vivo cytokine genes expression in chickens after challenge with Salmonella typhimurium lipopolysaccharide and modulation by dietary n--3 polyunsaturated fatty acids.

We studied the effects of Salmonella typhimurium lipopolysaccharide (LPS) on in vivo cytokine mRNA levels in chickens, and investigated whether these levels could be altered by different nutrients. Two hundred and forty chicks were assigned in a 2 x 4 factorial design of treatments. Factors were intravenous injection with S. typhimurium LPS, or saline (control), and four dietary fat sources: corn oil (CO), linseed oil (LO), menhaden oil and beef tallow (BT). Two hours after injection birds were killed and their spleens removed for RNA extraction. Quantitative real-time RT-PCR assays for mRNA of chicken IFN-gamma, IL-6, IL-8, IL-15, IL-18 and 28S rRNA were used to obtain the in vivo splenic cytokine profiles. Expression levels of IL-6, IL-8, IL-18 and IFN-gamma mRNA increased, but IL-15 mRNA decreased 2h after challenge with LPS compared with saline controls. In saline-injected control chickens, the dietary oil source did not affect the splenic mRNA level of any cytokine. In LPS challenged chickens IFN-gamma mRNA was significantly higher in the chickens fed the fish oil enriched diet compared with the LO, CO and BT enriched diets. The present data imply that avian IL-15 has, at least partially, a different function compared to its mammalian counterpart, and in addition, chicken innate immune responses might be affected differently by n-3 PUFA compared to mammals.

Animals↗