Human metapneumovirus keeps dendritic cells from priming antigen‐specific naive T cells

Summary Human metapneumovirus (h MPV ) is the second most common cause of acute lower respiratory tract infections in children, causing a significant public health burden worldwide. Given that h MPV can repeatedly infect the host without major antigenic changes, it has been suggested that h MPV may have evolved molecular mechanisms to impair host adaptive immunity and, more specifically, T ‐cell memory. Recent studies have shown that h MPV can interfere with superantigen‐induced T ‐cell activation by infecting conventional dendritic cells ( DC s). Here, we show that h MPV infects mouse DC s in a restricted manner and induces moderate maturation. Nonetheless, h MPV ‐infected DC s are rendered inefficient at activating naive antigen‐specific CD 4 + T cells ( OT ‐II), which not only display reduced proliferation, but also show a marked reduction in surface activation markers and interleukin‐2 secretion. Decreased T ‐cell activation was not mediated by interference with DC–T ‐cell immunological synapse formation as recently described for the human respiratory syncytial virus (hRSV), but rather by soluble factors secreted by h MPV ‐infected DC s. These data suggest that although h MPV infection is restricted within DC s, it is sufficient to interfere with their capacity to activate naive T cells. Altogether, by interfering with DC function and productive priming of antigen‐inexperienced T cells, h MPV could impair the generation of long‐term immunity.