Tregs in infection and vaccinology: heroes or traitors?
Bottom Line: The development of effective vaccines against life-threatening pathogens in human diseases represents one of the biggest challenges in biomedical science.Yet, while our immune system is mostly effective in eliminating or controlling a diverse range of microorganisms, its responses are incomplete or somewhat limited in several other cases.Different strategies have been pursued to circumvent Treg activity during immunization, but the lack of specific tools for their study has led sometimes to controversial conclusions.
Affiliation: Institute for Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, Medical School Hanover-MHH-Helmholtz Centre for Infection Research-HZI, Hanover, Germany.Show MeSH
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Mentions: Foxp3+ Tregs have been shown to mediate a constant equilibrium between pathogens and the host, in order to minimize exuberant immune responses and to maintain tissue integrity (Belkaid and Tarbell, 2009). Tregs suppress immune responses, thereby providing a window of opportunity for a pathogen to persist and prevail in the host. Alternatively, Tregs can also be subjected to regulation themselves as demonstrated in a Toxoplasma gondii model (Oldenhove et al., 2009). The underlying mechanisms controlling this behaviour leave room for intense speculation. Current knowledge in the field suggests that Tregs may either directly be activated by Toll‐like receptor (TLR) ligands or indirectly via secreted immunochemical cues from antigen presenting cells and T cells generated during infection (Pasare and Medzhitov, 2003). In addition, after infection the micro‐environment may also influence the fate of Tregs to determine the outcome of an immune response towards tolerance or immunity (Oldenhove et al., 2009). This paradoxical role of Tregs in host–pathogen interaction remains somewhat enigmatic, and the underlying mechanisms that control Tregs in an infectious setting may need further clarity. In this section, we discuss current knowledge involving interactions between Tregs and different microbial and parasitic pathogens and highlight niches in the role of Tregs during infection that could be subjected to manipulation during vaccine development (Fig. 1).
Affiliation: Institute for Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, Medical School Hanover-MHH-Helmholtz Centre for Infection Research-HZI, Hanover, Germany.