Chronic bystander infections and immunity to unrelated antigens

Abstract

Chronic infections with persistent pathogens such as helminths, mycobacteria, Plasmodium, and hepatitis viruses affect more than a third of the human population and are associated with increased susceptibility to other pathogens as well as reduced vaccine efficacy. Although these observations suggest an impact of chronic infections in modulating immunity to unrelated antigens, little is known regarding the underlying mechanisms. Here, we summarize evidence of the most prevalent infections affecting immunity to unrelated pathogens and vaccines, and discuss potential mechanisms of how different bystander chronic infections might impact immune responses. We suggest that bystander chronic infections affect different stages of host responses and may impact transmission and recognition of other pathogens, innate immune responses, priming and differentiation of adaptive effector responses, as well as the development and maintenance of immunological memory. Further understanding of the immunological effects of coinfection should provide opportunities to enhance vaccine efficacy and control of infectious diseases.

Figure 1. Potential mechanisms by which bystander chronic infections may affect immune responses to unrelated antigens

Bystander chronic infections, such as helminths, malaria, tuberculosis and viral hepatitis may affect different stages of a developing immune response to unrelated pathogens or vaccines. a) Pathogen entry though mucosal/epithelial barriers or vaccine uptake is illustrated as an event that may be altered by bystander chronic pathogens. Dysregulation of innate immune responses and reduced production of early anti-microbial mediators could impact initial pathogen replication. b) Reduced or altered APC function including antigen processing and presentation, co-stimulation and cytokine production may alter initial lymphocyte priming. c) Skewed lymphocyte differentiation could result in altered cytokine production, dysregulated humoral responses and reduced cytotoxicity, manifesting in defective or altered effector functions. d) Effects on memory B and T cell development and maintenance may occur, but it remains unclear whether these are direct effects on memory B and T cell differentiation after the effector phase or reflect alterations in the early stages of the immune response.