Filariae-Retrovirus Co-infection in Mice is Associated with Suppressed Virus-Specific IgG Immune Response and Higher Viral Loads

Abstract

Worldwide more than 2 billion people are infected with helminths, predominantly in developing countries. Co-infections with viruses such as human immunodeficiency virus (HIV) are common due to the geographical overlap of these pathogens. Helminth and viral infections induce antagonistic cytokine responses in their hosts. Helminths shift the immune system to a type 2-dominated immune response, while viral infections skew the cytokine response towards a type 1 immune response. Moreover, chronic helminth infections are often associated with a generalized suppression of the immune system leading to prolonged parasite survival, and also to a reduced defence against unrelated pathogens. To test whether helminths affect the outcome of a viral infection we set up a filarial/retrovirus co-infection model in C57BL/6 mice. Although Friend virus (FV) infection altered the L. sigmodontis-specific immunoglobulin response towards a type I associated IgG2 isotype in co-infected mice, control of L. sigmodontis infection was not affected by a FV-superinfection. However, reciprocal control of FV infection was clearly impaired by concurrent L. sigmodontis infection. Spleen weight as an indicator of pathology and viral loads in spleen, lymph nodes (LN) and bone marrow (BM) were increased in L. sigmodontis/FV-co-infected mice compared to only FV-infected mice. Numbers of FV-specific CD8+ T cells as well as cytokine production by CD4+ and CD8+ cells were alike in co-infected and FV-infected mice. Increased viral loads in co-infected mice were associated with reduced titres of neutralising FV-specific IgG2b and IgG2c antibodies. In summary our findings suggest that helminth infection interfered with the control of retroviral infection by dampening the virus-specific neutralising antibody response.

Rbpj expression in regulatory T cells is critical for restraining TH2 responses

“…Normally, immune competent mice mount a canonical T H 2 response and resolve the infection within 2–4 weeks 22 . Final expulsion of parasites from the intestine is predominantly mediated by IL-9 and activated mucosal mast cells 23 . Especially, Foxp3 + T reg cells have been shown to expand following S. ratti infection 24 .…”

The Influence of Parasite Infections on Host Immunity to Co-infection With Other Pathogens

“…This raises the suggestion that individuals co-infected with hookworms and HIV are at a distinct immunologic disadvantage when compared to those infected with HIV alone. This hypothesis has been experimentally tested in mice using a helminth/retrovirus co-infection model ( 88 ). Although the ability of the mice to control the L. sigmodontis infection was not affected in the co-infected mice, helminth infection did interfere with the host's ability to the control of the viral infection.…”

Highlighting the Relevance of CD8+ T Cells in Filarial Infections

“…The immunomodulatory benefits of helminths are being exploited for therapeutic purposes against inflammatory bowel diseases and autoimmunity ( 51 ). The filarial immuno-regulatory influence on disease progression and control has been demonstrated with several conditions, including filarial- plasmodium co-infection ( 52 ), filarial- mycobacterium co-infection ( 53 ), filarial-virus co-infections ( 54 ) and allergic reactions ( 55 ).…”

“…On the role of CD8 + T cells in filarial-immunoregulation of viral infections, a considerable gap remains. Dietze et al ( 54 ) studied the immunomodulatory effects of filaria-virus co-infection using an Litosomodes sigmodontis -Friend virus (FV) co-infected mice model. Both filaria-specific and viral-specific humoral responses were diminished, but no effect was found on CD8 + T cell response to FV infections.…”