Immune control of lethal Nipah virus infection: the critical role of host macrophages

Nipah virus (NiV) is highly pathogenic zoonotic paramyxovirus of Henipavirus genus that causes recurrent human outbreaks in South-East Asia, with a lethality of 40-75%. Immunopathogenesis associated to this emerging virus is still poorly understood and the role of different components of the immune response in the control of infection remains unknown. In contrast to many other mammalian species, wild type mice are resistant to NiV infection, due to an efficient type-I interferon response. We have analysed the role of various immune cell populations in the control of NiV infection and demonstrated the critical role of T lymphocytes but neither B lymphocytes nor NK cells were primordial. In addition, the depletion of phagocytes in mice by injection of clodronate liposomes resulted in dramatical increase of their susceptibility to NiV infection. Moreover, using CD169-DTR transgenic mice we show here that the specific depletion of CD169+ macrophages results in an increased susceptibility of mice to NiV challenge, highlighting the important role of this cell population. Finally, in NiV-infected African green monkeys, which closely resemble severe human Nipah disease, the production of virus-induced type-I and -II interferons was followed with an important increase of CD169+ cells in the blood and lungs, with some of them being NiV-infected. As CD169+ macrophages have been described to play an important role at the crossroads between innate and adaptive immunity in various infections, these results reveal their potentially determining role during NiV infection as well, which may help to better understand this highly lethal infectious disease.