BackgroundHTLV-I associated adult T-cell leukemia/lymphoma (ATL) carries a dismal prognosis due to chemo-resistance and immuno-compromised micro-environment. The combination of zidovudine and interferon-alpha (IFN) significantly improved survival in ATL. Promising results were reported by adding arsenic trioxide to zidovudine and IFN.ResultsHere we assessed Th1/Th2/Treg cytokine gene expression profiles in 16 ATL patients before and 30 days after treatment with arsenic/IFN/zidovudine, in comparison with HTLV-I healthy carriers and sero-negative blood donors. ATL patients at diagnosis displayed a Treg/Th2 cytokine profile with significantly elevated transcript levels of Foxp3, interleukin-10 (IL-10), and IL-4 and had a reduced Th1 profile evidenced by decreased transcript levels of interferon-γ (IFN-γ) and IL-2. Most patients (15/16) responded, with CD4+CD25+ cells significantly decreasing after therapy, paralleled by decreases in Foxp3 transcript. Importantly, arsenic/IFN/zidovudine therapy sharply diminished IL-10 transcript and serum levels concomittant with decrease in IL-4 and increases in IFN-γ and IL-2 mRNA, whether or not values were adjusted to the percentage of CD4+CD25+ cells. Finally, IL-10 transcript level negatively correlated with clinical response at Day 30.ConclusionsThe observed shift from a Treg/Th2 phenotype before treatment toward a Th1 phenotype after treatment with arsenic/IFN/zidovudine may play an important role in restoring an immuno-competent micro-environment, which enhances the eradication of ATL cells and the prevention of opportunistic infections.

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In vitro and in vivo experiments were conducted to study the effects of synbiotic supplementation on Salmonella enterica ser. Enteritidis (SE) proliferation, cecal content load, and broiler carcass contamination. Lactobacillus reuteri, Enterococcus faecium, Bifidobacterium animalis, and Pediococcus acidilactici culture supernatants decreased (P < 0.05) the in vitro proliferation of SE at 1:1 supernatant: pathogen dilution. A total of 240 Cobb-500 broiler chicks were randomly allotted to three treatment groups (8 replicates/group with 10 birds/replicate): control (basal diet), antibiotic (Virginiamycin at 20 mg/kg feed), synbiotic (PoultryStar® ME at 0.5 g/kg feed containing L. reuteri, E. faecium, B. animalis, P. acidilactici and a Fructooligosaccharide) from day of hatch. At 21 d of age, all birds in experimental groups were orally inoculated with 250 μl of 1 X 109 CFU SE. Antibiotic supplementation increased (P < 0.05) body weight and feed consumption, compared to the control group. Birds in the synbiotic supplementation had intermediate body weight and feed consumption that were not significantly different from both the control and antibiotic group at 42 d of age in SE infected birds. No significant effects were observed in feed efficiency at 42 d of age among the groups. Antibiotic and synbiotic supplementation decreased (P < 0.05) SE load in cecal contents by 0.90 and 0.85 log units/ g and carcass SE load by 1.4 and 1.5 log units/mL of rinsate compared to the control group at 42 d of age (21 dpi). The relative abundance of IL-10, IL-1, TLR-4, and IFNγ mRNA was decreased (P < 0.05) in the antibiotic and synbiotic supplementation groups compared to the control birds at 42 d of age (21 dpi). It can be concluded that synbiotic supplementation decreased SE proliferation in vitro and decreased SE load in the cecal contents and broiler carcass.

Campylobacter is one of the major foodborne pathogens causing bacterial gastroenteritis worldwide. The immune response of broiler chickens to C. jejuni is under-researched. This study aimed to characterize the immune response of chickens to Campylobacter jejuni colonization. Birds were challenged orally with 0.5 mL of 2.4 x 108 CFU/mL of Campylobacter jejuni or with 0.5 mL of 0.85% saline. Campylobacter jejuni persisted in the ceca of challenged birds with cecal colonization reaching 4.9 log10 CFU/g on 21 dpi. Campylobacter was disseminated to the spleen and liver on 7 dpi and was cleared on 21 dpi from both internal organs. Challenged birds had a significant increase in anti-Campylobacter serum IgY (14&21 dpi) and bile IgA (14 dpi). At 3 dpi, there was a significant suppression in T-lymphocytes derived from the cecal tonsils of birds in the challenge treatment when compared to the control treatment after 72 h of ex vivo stimulation with Con A or C. jejuni. The T-cell suppression on 3 dpi was accompanied by a significant decrease in LITAF, K60, CLAU-2, IL-1β, iNOS, and IL-6 mRNA levels in the ceca and an increase in nitric oxide production from adherent splenocytes of challenged birds. In addition, on 3 dpi, there was a significant increase in CD4+ and CD8+ T lymphocytes in the challenge treatment. On 14 dpi, both pro and anti-inflammatory cytokines were upregulated in the spleen, and a significant increase in CD8+ T lymphocytes in Campylobacter-challenged birds’ ceca was observed. The persistence of C. jejuni in the ceca of challenged birds on 21 dpi was accompanied by an increase in IL-10 and LITAF mRNA levels, an increase in MNC proliferation when stimulated ex-vivo with the diluted C. jejuni, an increase in serum specific IgY antibodies, an increase in both CD4+ and CD8+ cells, and a decrease in CD4+:CD8+ cell ratio. The balanced Th1 and Th2 immune responses against C. jejuni might explain the ceca’s bacterial colonization and the absence of pathology in Campylobacter-challenged birds. Future studies on T lymphocyte subpopulations should elucidate a pivotal role in the persistence of Campylobacter in the ceca.

Studies were conducted to determine the efficacy of synbiotic applications to combat the negative effects of necrotic enteritis ( NE ). An in vitro study was conducted to test the effect of probiotics species supernatants to decrease Clostridium perfringens ( CP ) proliferation. Lactobacillus reuteri , Enterococcus faecium , Bifidobacterium animalis , and Pediococcus acidilactici culture supernatants decreased the proliferation of CP at 1:1 supernatant-to-pathogen dilution in vitro. Two in vivo studies were conducted to determine the in vivo response of synbiotic supplementation containing the aforementioned probiotic strains on broiler production performance and caecal CP load in broilers induced with NE infection. In experiment 1, 75 broiler chicks were randomly allotted to 3 treatment groups, control (basal diet), ionophore (Salinomycin), and synbiotic (PoultryStar me), from day of hatch, and NE was induced in all birds. There were no significant treatment effects on BW, feed consumption, and feed gain ratio. However, at 35 D, ionophore or synbiotic supplementation increased ( P < 0.05) villi height and decreased interleukin ( IL )-1 mRNA abundance, while synbiotic supplementation increased ( P < 0.05) IL-10 mRNA abundance compared with the control group, respectively. In experiment 2, 360 broiler chicks were randomly allotted to 3 treatments, an unchallenged negative control (control; basal diet), challenged positive control (NE; basal diet), or NE + synbiotic group (synbiotic). At both 21 and 42 D of age, NE birds had decreased ( P < 0.05) BW, feed conversion, and jejunal villi height compared with control, while NE + synbiotic birds were not different from control groups. At 42 D of age, NE birds had 2.2 log/g increased CP in the ceca contents compared with control, while synbiotic birds had CP load that was not different than that of the control group. NE + synbiotic birds had significantly greater amounts of bile anti-CP IgA than the control and NE groups. It can be concluded that synbiotic supplementation decreased CP proliferation in vitro and caecal CP load in vivo while improving production parameters during an NE infection in broilers.