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.
Highlights
One third of the world population is infected with helminths [1]
To analyse helminth-virus co-infections we first infected C57BL/6 mice with L. sigmodontis by exposing the animals to infected mites. 14 days later, when L4 were present in the pleural cavity, the mice were superinfected with a high dose of Friend virus (FV)
The time point of L. sigmodontis infection was chosen since the IgG response to a model antigen and the proliferation of ovalbuminspecific CD4+ TCR transgenic T cells is diminished in day 14 L. sigmodontis-infected mice [36, 37]
Summary
One third of the world population is infected with helminths [1]. Helminth endemic areas overlap with high-risk areas for viral infections in the developing countries [1,2,3]. Helminth-induced immunosuppression is mediated by the induction of regulatory cell types such as regulatory T (Treg) and B cells, negative regulatory receptors such as cytotoxic T lymphocyte associated protein-4 [5, 6], B and T lymphocyte attenuator [7] and programmed death-1 [8], and antiinflammatory cytokines such as interleukin-10 and transforming growth factor-β [9] This helminth-mediated downregulation of immunity affects immune responses to unrelated ‘third party’ antigens and can be detrimental for the host in terms of vaccinations or co-infections [9, 10]. Neutralising antibodies are crucial for the control of FV during acute infection and for vaccine-induced protection against FV [27,28,29,30]
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