Delayed development of virus-specific immune response has been observed in pigs infected with the porcine reproductive and respiratory syndrome virus (PRRSV). Several studies support the hypothesis that the PRRSV is capable of modulating porcine immune system, but the mechanisms involved are yet to be defined. In this study, we evaluated the induction of T regulatory cells by PRRSV-infected dendritic cells (DCs). Our results showed that PRRSV-infected DCs significantly increased Foxp3(+)CD25(+) T cells, an effect that was reversible by IFN-alpha treatment, and this outcome was reproducible using two distinct PRRSV strains. Analysis of the expressed cytokines suggested that the induction of Foxp3(+)CD25(+) T cells is dependent on TGF-beta but not IL-10. In addition, a significant up-regulation of Foxp3 mRNA, but not TBX21 or GATA3, was detected. Importantly, our results showed that the induced Foxp3(+)CD25(+) T cells were able to suppress the proliferation of PHA-stimulated PBMCs. The T cells induced by the PRRSV-infected DCs fit the Foxp3(+)CD25(+) T helper 3 (Th3) regulatory cell phenotype described in the literature. The induction of this cell phenotype depended, at least in part, on PRRSV viability because IFN-alpha treatment or virus inactivation reversed these effects. In conclusion, this data supports the hypothesis that the PRRSV succeeds to establish and replicate in porcine cells early post-infection, in part, by inducing Th3 regulatory cells as a mechanism of modulating the porcine immune system.

Porcine reproductive and respiratory syndrome virus (PRRSV) infects mature dendritic cells (mDCs)derived from porcine monocytes and matured with lipopolysaccharide. The infection of mDCs induced apoptosis, reduced the expression of CD80/86 and major histocompatibility complex class II molecules, and increased the expression of interleukin-10, thus suggesting that such mDC modulation results in the impairment of T-cell activation.Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped RNA virus that belongs to the Arteriviridae family (15). PRRSV is responsible for significant economic losses and is the cause of the most important infectious disease affecting swine production worldwide. PRRSV infects pigs of different ages, and cells supporting PRRSV replication are located in different organs and tissues, with alveolar macrophages being the principal cell type that supports replication. Apoptotic cells have been associated with PRRSV infection, and they are distributed in different infected tissues, including lung, testes, and lymph node (21,22). Protective immunity against PRRSV is not clearly understood. A delay in the appearance of the cellular immune response suggests that PRRSV infection involves a mechanism of immunosuppression or immunomodulation (18). Recently, it was reported that PRRSV infects and interferes with some functions of immature monocyte-derived dendritic cells (DCs) (3,11,27), as evidenced by the down-regulation of alpha interferon (IFN-␣) mRNA and the up-regulation of IFN-␤ and tumor necrosis factor alpha (TNF-␣) mRNA without changes in the production of interleukin-10 (IL-10), . No report exists, however, on the effects of PRRSV on mature DCs (mDCs). In this paper, we report the effects of PRRSV on mature porcine monocyte-derived DCs. Our results show that PRRSV replicated in mDCs, induced apoptosis, down-regulated the expression of CD80/86 costimulatory and major histocompatibility complex class II (MHC-II) molecules, reduced the allogeneic stimulation of T cells, and up-regulated the expression of IL-10 (mRNA and protein).The PRRSV strain NVSL 97-7895 (GenBank accession no. AY545985) was propagated in MARC-145 cells, and the supernatant was collected, titrated, and stored at Ϫ70°C. Porcine alveolar macrophages (PAM) were collected and maintained as described previously (14). The following monoclonal antibodies were used: for MHC-II, MSA3; for CD172a, SWC3(74-22-15); and for CD14, CAM36A; all were from VMRD (Pullman, WA). Other key reagents included mouse immunoglobulin G (IgG) Fc-human cytotoxic T-lymphocyte-associated antigen 4 fusion protein (501-820; Ancell, Bayport, MN), goat anti-mouse IgG-fluorescein isothiocyanate (IgG-FITC) (Southern Biotech), and recombinant porcine IL-4 (PSC0045) and recombinant porcine granulocyte-macrophage colony-stimulating factor (PSC2015) from Biosource International (Camarillo, CA). Escherichia coli O55:B5 lipopolysaccharide (LPS) and PCR primers and probe were from Sigma (St. Louis, MO). Blood samples were taken from 4-to 8-week-old...

The aim of this study was to characterize the immune responses of DCs after infection with four different EU strains of PRRSV and whether they show any ability to immunomodulate T cells activation. Our results show that all EU strains can efficiently infect and replicate in DCs. Nevertheless, SLA-II levels remained unaltered in DC infected by all EU PRRSV strains, whereas SLA-I expression was only reduced when strain 2992 was used. IL-10 production was induced by three EU PRRSV strains, being strain 2992 the highest inducer. However, no induction of Treg cells, measured by CD25 and Foxp3 expression on lymphocytes co-cultured with infected DCs, was found. TGF-beta induction was not detected in DC infected with any EU strain tested. In conclusion, DCs infected with EU PRRSV strains exhibited an unbalanced ability to stimulate T cell response and was strain dependent. However, Treg cells were not induced, at least in vitro.

Annual mortality rates due to infectious diarrhea are about 2.2 million; children are the most vulnerable age group to severe gastroenteritis, representing group A rotaviruses as the main cause of disease. One of the main factors of rotavirus pathogenesis is the NSP4 protein, which has been characterized as a viral toxin involved in triggering several cellular responses leading to diarrhea. Furthermore, the rotavirus protein NSP1 has been associated with interferon production inhibition by inducing the degradation of interferon regulatory factors IRF3, IRF5, and IRF7. On the other hand, probiotics such as Bifidobacterium and Lactobacillus species in combination with prebiotics such as inulin, HMO, scGOS, lcFOS have been associated with improved generalized antiviral response and anti-rotavirus effect by the reduction of rotavirus infectivity and viral shedding, decreased expression of NSP4 and increased levels of specific anti-rotavirus IgAs. Moreover, these probiotics and prebiotics have been related to shorter duration and severity of rotavirus diarrhea, to the prevention of infection and reduced incidence of reinfections. In this review we will discuss in detail about the rotavirus pathogenesis and immunity, and how probiotics such as Lactobacillus and Bifidobacterium species in combination with prebiotics have been associated with the prevention or modulation of rotavirus severe gastroenteritis.