MyD88-dependent influx of monocytes and neutrophils impairs lymph node B cell responses to chikungunya virus infection via Irf5, Nos2 and Nox2

McCarthy, Mary K.; Reynoso, Glennys V.; Winkler, Emma S.; Mack, Matthias; Diamond, Michael S.; Hickman, Heather D.; Morrison, Thomas E.

Arthritogenic alphaviruses, including chikungunya virus (CHIKV), Mayaro virus, and Ross River virus, are emerging public health concerns. CHIKV, in particular, re-emerged in 2004 to cause massive outbreaks of disease affecting millions [8] . Acute CHIKV disease presents with rapid onset of fever and rash, with severe joint swelling and arthralgia. A high proportion of individuals develop chronic arthralgia or arthritis that lasts for months to years after initial infection [9] . Following CHIKV infection, the humoral response reduces acute disease severity and controls viremia [10] , and passive transfer of immune serum or monoclonal antibodies protects from fatal CHIKV disease [11] [12] [13] . However, B cells and Ab are unable to mediate complete clearance of CHIKV from all sites of infection [14] [15] [16] [17] [18] [19] [20] [21] [22] . Thus, chronic CHIKV disease in musculoskeletal tissue may be driven by failure of the adaptive immune response to prevent or control viral persistence.