Effects of chronic heat stress on immune responses of the foot-and-mouth disease DNA vaccination.
ABSTRACT The main purpose of this study was to assess the effects of chronic heat stress (CHS) on humoral and cellular responses of DNA vaccination. Mice with the CHS were exposed to a temperature set at 38 +/- 1 degrees C, 2h per day, for 35 days, and mice with thermoneutral (TN) temperature were maintained at 24 +/- 1 degrees C for the same period of time. Both groups of mice were immunized with a DNA vaccine-expressed viruscapsid protein 1 (VP1) of foot-and-mouth disease virus (FMDV), and we tested their antigen-specific humoral and cellular responses during the treatments. Compared with the TN group, titers of total Imunoglobulin G (IgG) and IgG1 and expression of interleukin 4 (IL-4) in CD4(+) cells of CHS group were not affected significantly. In contrast, the levels of IgG2a, T cell proliferations, and expression of interferon-gama (IFN-gamma) in both CD4(+) and CD8(+) cells were suppressed significantly, and cytotoxic T-lymphocyte (CTL) responses in vivo were also weakened by the CHS condition. These results indicate that the CHS treatment has negatively affected the immune responses of DNA vaccination and particularly impaired to the cell-mediated responses. It suggests that vaccination in animals is affected by the changes of ambient temperature.
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ABSTRACT: Chronic heat stress (CHS) is known to have negative impacts on the immune responses in animals and increases their susceptibility to infections including the highly pathogenic avian influenza virus H5N1. However, the role of regulatory T cells (Tregs) in CHS immunosuppression remains largely undefined. In this study, we demonstrated a novel mechanism by which CHS suppressed both Th1 and Th2 immune responses and dramatically decreased the protective efficacy of the formalin-inactivated H5N1 vaccine against H5N1 influenza virus infection. This suppression was found to be associated with the induced generation of CD4(+)CD25(+)FoxP3(+) Tregs and the increased secretions of IL-10 and TGF- β in CD4(+) T cells. Adoptive transfer of the induced Tregs also suppressed the protective efficacy of formalin-inactivated H5N1 virus immunization. Collectively, this study identifies a novel mechanism of CHS immunosuppression mediated by regulating CD4(+)CD25(+)Foxp3(+) Tregs.09/2013; 2013:160859. DOI:10.1155/2013/160859
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ABSTRACT: Chinese hamster lung fibroblasts V79 cells were treated with heat stress for 4 weeks with short duration (15 min) heat shock every alternate day in culture. It was observed that Hsp 70 and the antioxidant enzyme MnSOD became overexpressed during the chronic heat stress period. Both p38 MAPK and Akt became phosphorylated by chronic heat stress exposure. Simultaneous exposure to SB203580, a potent and specific p38MAPK inhibitor drastically inhibited the phosphorylation of p38MAPK and Akt. Furthermore, exposure to SB203580 also blocked the increase in Hsp70 and MnSOD levels and the elevated SOD activity brought about by chronic heat stress. Heat shock factor 1 (HSF1) transcriptional activity and nuclear translocation of HSF1 were prominently augmented by chronic heat stress, and this amplification is markedly reduced by concomitant exposure to SB203580. Also, activations of p38MAPK and Akt and upregulations of Hsp70 and MnSOD were observed on exposure to heat shock for a single exposure of longer duration (40 min). siRNA against p38MAPK notably reduced Akt phosphorylation by single exposure to heat stress and drastically diminished the rise in Hsp70 and MnSOD levels. Similarly, siRNA against Akt also eliminated the augmentation in Hsp70 and MnSOD levels but p38MAPK levels remained unaffected. Heat stress produced reactive oxygen species (ROS) in V79 fibroblasts. N-acetyl cysteine blocked the increase in phosphorylation of p38MAPK, amplification of Hsp70, and MnSOD levels by heat stress. Therefore, we conclude that heat stress-activated p38MAPK which in turn activated Akt. Akt acted downstream of p38MAPK to increase Hsp70 and MnSOD levels.Concise summary: Thermal injury of the skin over a long period of time has been associated with development of cancerous lesions. Also, in many cancers, the cytoprotective genes Hsp70 and MnSOD have been found to be overexpressed. Therefore, we considered it important to identify the signaling elements upstream of the upregulated survival genes in heat stress. We conclude that heat stress activated p38MAPK which in turn activated Akt. Akt mediated an augmentation in Hsp70 and MnSOD levels working downstream of p38MAPK.Cell Stress and Chaperones 04/2009; 14(6):579-89. DOI:10.1007/s12192-009-0109-x · 2.54 Impact Factor
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ABSTRACT: Chronic heat stress (CHS) can negatively affect immune response in animals. In this study we assessed the effects of CHS on host innate immunity and avian influenza virus H5N1 infection in mice. Mice were divided into two groups: CHS and thermally neutral (TN). The CHS treatment group exhibited reduced local immunity in the respiratory tract, including the number of pulmonary alveolar macrophages and lesions in the nasal mucosa, trachea, and lungs. Meanwhile, CHS retarded dendritic cells (DCs) maturation and reduced the mRNA levels of IL-6 and IFN-β significantly (P < .05). After the CHS treatment, mice were infected with H5N1 virus. The mortality rate and viral load in the lungs of CHS group were higher than those of TN group. The results suggest that the CHS treatment could suppress local immunity in the respiratory tract and innate host immunity in mice significantly and moderately increased the virulence in H5N1-infected mice.BioMed Research International 05/2011; 2011(1110-7243):367846. DOI:10.1155/2011/367846 · 2.71 Impact Factor