Interferon-α induces unabated production of short-lived plasma cells in pre-autoimmune lupus-prone (NZB×NZW)F1 mice but not in BALB/c mice

IFN-α is known to play a critical role in the pathogenesis of systemic lupus erythematosus (SLE), but the mechanisms remain unclear. We previously showed that within weeks, exposure to IFN-α in vivo induces lupus in pre-autoimmune lupus-prone NZB×NZW F1 (NZB/W) but not in BALB/c mice. In the current study, we show that in vivo expression of IFN-α induces sustained B-cell proliferation in both BALB/c and NZB/W mice. In NZB/W but not BALB/c mice, B-cell proliferation was accompanied by a rapid and unabated production of autoantibody-secreting cells (ASCs) in secondary lymphoid organs, suggesting that a B-cell checkpoint is altered in the autoimmune background. The majority (>95%) of ASCs elicited in IFN-α-treated NZB/W mice were short-lived and occurred without the induction of long-lived plasma cells. A short course of cyclophosphamide caused a sharp drop in IFN-α-elicited short-lived plasma cells, but the levels recovered within days following termination of treatment. Thus, our work provides new insights into effectiveness and limitations of the current SLE therapies.     

Inhibition of IL-4 but not IFN-γ production by splenocytes of mice immunized with ovalbumin after oral administration of 5-hydroxymethylfurfural

5-Hydroxymethylfurfural (5-HMF) is one of the most important products of maillard reaction. This study sought to elucidate the immunomodulatory effect of 5-HMF by evaluating IFN-γ and IL-4 production in BALB/c mice sensitized with ovalbumin (OVA). Four groups of BALB/c mice (n?=?5 for each group) including control, vehicle and two 5-HMF (188 and 750?mg/kg?bw) treatment groups were studied. Interleukin-4(IL-4) and interferon gamma (IFN-γ) levels were measured in culture supernatants of spleen cells using enzyme-linked immunosorbent assay. It was found that the IL-4 level was significantly suppressed in 5-HMF treatment groups compared with the vehicle group (P?P?相似文献   

Infection with conditionally virulent Streptococcus pneumoniae Δpab strains induces antibody to conserved protein antigens but does not protect against systemic infection with heterologous strains

Avirulent strains of a bacterial pathogen could be useful tools for investigating immunological responses to infection and potentially effective vaccines. We have therefore constructed an auxotrophic TIGR4 Δpab strain of Streptococcus pneumoniae by deleting the pabB gene Sp_0665. The TIGR4 Δpab strain grew well in complete medium but was unable to grow in serum unless it was supplemented with para-aminobenzoic acid (PABA). The TIGR4 Δpab strain was markedly attenuated in virulence in mouse models of S. pneumoniae nasopharyngeal colonization, pneumonia, and sepsis. Supplementing mouse drinking water with PABA largely restored the virulence of TIGR4 Δpab. An additional Δpab strain constructed in the D39 capsular serotype 2 background was also avirulent in a sepsis model. Systemic inoculation of mice with TIGR4 Δpab induced antibody responses to S. pneumoniae protein antigens, including PpmA, PsaA, pneumolysin, and CbpD, but not capsular polysaccharide. Flow cytometry demonstrated that IgG in sera from TIGR4 Δpab-vaccinated mice bound to the surface of TIGR4 and D39 bacteria but not to a capsular serotype 3 strain, strain 0100993. Mice vaccinated with the TIGR4 Δpab or D39 Δpab strain by intraperitoneal inoculation were protected from developing septicemia when challenged with the homologous S. pneumoniae strain. Vaccination with the TIGR4 Δpab strain provided only weak or no protection against heterologous challenge with the D39 or 0100993 strain but did strongly protect against a TIGR4 capsular-switch strain expressing a serotype 2 capsule. The failure of cross-protection after systemic vaccination with Δpab bacteria suggests that parenteral administration of a live attenuated vaccine is not an attractive approach for preventing S. pneumoniae infection.     

Evaluation of a DNA vaccine candidate co-expressing GP3 and GP5 of porcine reproductive and respiratory syndrome virus (PRRSV) with interferon α/γ in immediate and long-lasting protection against HP-PRRSV challenge

Porcine reproductive and respiratory syndrome virus (PRRSV) has become one of the most economically important diseases to the global pork industry. Current vaccination strategies only provide a limited protective efficacy. In this study, a DNA vaccine, pVAX1^?-??-??-GP35, co-expressing GP3 and GP5 of PRRSV with interferon ??/?? was constructed, and its immediate and long-lasting protection against highly pathogenic PRRSV (HP-PRRSV) challenge were examined in pigs. For immediate protection, the results showed that pVAX1^?-??-??-GP35 could provide partially protective efficacy, which was similar to the pVAX1^?-??-?? (expressing interferon ??/??). For long-lasting protection, pigs inoculated with pVAX1^?-??-??-GP35 developed significantly higher PRRSV-specific antibody response, T cell proliferation, IFN-??, and IL-4, than those vaccinated with pVAX1^?-GP35 (expressing GP3 and GP5 of PRRSV). Following homologous challenge with HP-PRRSV strain SD-JN, pigs inoculated with pVAX1^?-??-??-GP35 showed almost no clinical signs, no lung lesions, and significantly lower viremia, as compared to those in pVAX1^?-GP35 group. It indicated that pVAX1^?-??-??-GP35 could induce enhanced immune responses and provide both immediate and long-lasting protection against HP-PRRSV challenge in pigs. The DNA vaccine pVAX1^?-??-??-GP35 might be an attractive candidate vaccine for the prevention and control of HP-PRRSV infections.