Myd88 is required for an antibody response to retroviral infection.
Although retroviruses have been extensively studied for many years, basic questions about how retroviral infections are detected by the immune system and which innate pathways are required for the generation of immune responses remain unanswered. Defining these pathways and how they contribute to the anti-retroviral immune responses would assist in the development of more effective vaccines for retroviral pathogens such as HIV. We have investigated the roles played by CD11c(+) dendritic cells (DCs) and by Toll-like receptor (TLR) signaling pathways in the generation of an anti-retroviral immune response against a mouse retroviral pathogen, Friend murine leukemia virus (F-MLV). Specific deletion of DCs during F-MLV infection caused a significant increase in viral titers at 14 days post-infection, indicating the importance of DCs in immune control of the infection. Similarly, Myd88 knockout mice failed to control F-MLV, and sustained high viral titers (10(7) foci/spleen) for several months after infection. Strikingly, both DC-depleted mice and Myd88 knockout mice exhibited only a partial reduction of CD8(+) T cell responses, while the IgG antibody response to F-MLV was completely lost. Furthermore, passive transfer of immune serum from wild-type mice to Myd88 knockout mice rescued control of F-MLV. These results identify TLR signaling and CD11c(+) DCs as playing critical roles in the humoral response to retroviruses.
Browne
Edward P
EP
The Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, New York, New York, United States of America.
Littman
Dan R
DR
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005622:Friend murine leukemia virus / Q000276:immunology* / Q000502:physiology; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012192:Retroviridae Infections / Q000276:immunology* / Q000821:virology; D015398:Signal Transduction; D018709:Statistics, Nonparametric; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014412:Tumor Virus Infections / Q000276:immunology / Q000821:virology; D014779:Virus Replication
D000914:Antibodies, Viral; D039521:CD11c Antigen; D007074:Immunoglobulin G; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors