Interaction of Rotavirus with Human Myeloid Dendritic Cells

Abstract

Rotaviruses (RV) are responsible for the deaths of approximately 1,200 children daily worldwide (41). To develop new strategies for treating or preventing this disease, our laboratory is currently characterizing human virus-specific T and B cells in children and adults (16,23,24,48). We recently showed that healthy adults have very low frequencies of circulating CD4 ϩ and CD8ϩ RV-specific T cells that secrete gamma interferon (IFN-␥) (23, 48). Significantly higher frequencies of these cells were found in symptomatic RV-infected adults. Nonetheless, the frequencies of these cells in all groups of study volunteers were relatively low compared to the frequencies of T cells specific for other pathogens (23,48). Surprisingly, in RV-infected children, virus-specific CD4 ϩ and CD8 ϩ T cells that secreted IFN-␥, interleukin 13 (IL-13), or IL-4 were very low or undetectable. From these studies, we hypothesized that RV has developed mechanisms to evade the immune response (23). In agreement with this hypothesis, sterilizing immunity is not induced after primary RV infection (11, 53). However, children develop a lymphoproliferative response to RV after primary infection (36,40), and over 90% of adults have a response of IFN-␥-secreting T cells in response to RV (27). These results suggest that if RV has developed immune evasion mechanisms, they are only partial in RV-infected children and can eventually be overcome after multiple reinfections in adults.

Rotavirus acceleration of murine type 1 diabetes is associated with a T helper 1-dependent specific serum antibody response and virus effects in regional lymph nodes

“…Although their rarity precludes further experimental marker delineation, their variable CD4, CD8 and CD11b expression suggests that RRV associates with several cell subsets. A similar pattern of infectious rotavirus association with multiple subsets of APC occurs in diabetes-resistant mouse strains and human mononuclear cells [22,38,39]. The uptake of infectious rotavirus by CD3 −…”

Rotavirus Differentially Infects and Polyclonally Stimulates Human B Cells Depending on Their Differentiation State and Tissue of Origin

“…The vaccine strain RRV (G3 P [3]) and human virus Wa (G1 P1A [8]) were used to infect circulating and intestinal human B cells. Viruses were produced in MA104 cells as previously described (26,52), with minor modifications. Briefly, a semiconfluent monolayer of MA104 cells was washed three times with serum-free medium and infected at a multiplicity of infection (MOI) of 10 during 1 h at 37°C.…”

“…To produce mock-infected cells, the same process was performed without virus. The titer of the virus was determined with MA104 cells as previously described (52).…”

Virus-specific intestinal IFN-γ producing T cell responses induced by human rotavirus infection and vaccines are correlated with protection against rotavirus diarrhea in gnotobiotic pigs

“…This assay allows quantitation of HRV-specific IFN-γ producing T cells, at the single cell level [29]. Studies of the interaction of rotavirus with human myeloid dendritic cells (MDCs) demonstrated that intact peripheral blood mononuclear cell (PMNC) populations containing antigen presenting cells are equally efficient compared to rotavirus-infected MDC, in stimulating IFN-γ-producing rotavirus-specific effector-memory T cells [30]. Furthermore, the frequencies and patterns of cytokines produced by effector-memory CD4+ T cells after stimulation of peripheral blood MNC with the purified rhesus rotavirus (RRV) or MDC infected with RRV were similar.…”