Cutting Edge: Myeloid Complement C3 Enhances the Humoral Response To Peripheral Viral Infection

Abstract

HSV-1 is the causative agent of cutaneous lesions, commonly referred to as cold sores. Primary exposure to the virus ordinarily occurs through the periphery, in particular through abraded skin or mucosal membranes. Under certain circumstances (e.g., in neonatals or AIDS patients), the infection becomes disseminated, often with severe consequences. Spread of HSV-1 is limited by virus-specific Ab. The development of an efficient humoral response to the virus is dependent on innate immunity component complement C3. The liver is the major source of C3, but there are also extrahepatic origins of C3 such as lymphoid macrophages. In the present study, the significance of C3 synthesis by bone marrow-derived cells was assessed by the transfer of wild-type bone marrow into irradiated C3-deficient mice. Using these chimeric mice, extrahepatic C3 was determined sufficient to initiate specific Ab and memory responses to a peripheral HSV-1 infection.

The Vaccinia Virus Complement Control Protein Modulates Adaptive Immune Responses during Infection

“…Complement activation can also contribute to defense against viral infection by enhancing adaptive antibody (Ab) and T cell responses. Complement has been shown to enhance Ab responses to several viruses, including herpes simplex virus (HSV) (7,14,15,55,56), vesicular stomatitis virus (VSV) (44), and West Nile virus (WNV) (37,38). Recently, it has become clear that complement is also important for eliciting optimal T cell responses to several viral pathogens (10,24,37,50).…”

“…Despite compelling evidence that complement activation enhances Ab and T cell responses (7,10,14,15,23,24,37,44,50,55,56), it is unknown whether inhibition of complement by pathogens can also limit adaptive immune responses. VCP has been characterized as a virulence factor (20), but the mechanisms by which it contributes to the pathogenesis of VACV in vivo have not been fully defined.…”

Systemic humoral autoimmunity but joint‐specific inflammation: The syndrome of rheumatoid arthritis

“…The primary function of local synthesis of complement may be to alert the host to the presence of an infectious agent. Injecting preformed antibodies to initiate joint inflammation is not likely to closely mimic HSV infection of the skin, which is the one situation in which local synthesis has been shown to facilitate an adaptive immune response to this pathogen (19)(20)(21). Thus, these data do not eliminate a role for local synthesis of complement components in facilitating a de novo immune response.…”

“…The availability of C3 Ϫ/Ϫ mice has permitted performance of a series of interesting experiments to examine the role for extrahepatic C3 synthesis in immune responses (19)(20)(21). Bone marrow-derived cells provide sufficient local C3 synthesis for priming an adaptive antibody response.…”

“…Bone marrow-derived cells provide sufficient local C3 synthesis for priming an adaptive antibody response. Evidence supporting this hypothesis has come from the bone marrow chimera studies of C3 Ϫ/Ϫ mice (19)(20)(21). Radiation is used to eliminate the sensitive bone marrow cells in C3 Ϫ/Ϫ mice.…”