Interleukin-10 and immunity against prokaryotic and eukaryotic intracellular pathogens

Abstract

The generation of an effective immune response against an infection while also limiting tissue damage requires a delicate balance between pro- and anti-inflammatory responses. Interleukin-10 (IL-10) has potent immunosuppressive effects and is essential for regulation of immune responses. However, the immunosuppressive properties of IL-10 can also be exploited by pathogens to facilitate their own survival. In this minireview, we discuss the role of IL-10 in modulating intracellular bacterial, fungal, and parasitic infections. Using information from several different infection models, we bring together and highlight some common pathways for IL-10 regulation and function that cannot be fully appreciated by studies of a single pathogen.

Fig. 1.

The interplay between pathogen and host dictates the requirements for IL-10. The initial interaction between the pathogen and host likely dictates the necessity for the immunoregulatory role of IL-10. (A) If pathogen recognition leads to proinflammatory responses that can rapidly and successfully eradicate the pathogen, the anti-inflammatory properties of IL-10 are minimal and an IL-10 blockade or removal has little effect on disease outcome. (B) If pathogen recognition triggers a strong inflammatory response with abundant TNF, IL-10 is essential to counter this reaction and prevent tissue damage. The removal of IL-10 leads to a severe immunopathology that is frequently lethal. (C) For pathogens that are able to avoid killing by host cells, a balance is established between the generation of proinflammatory responses to eradicate the pathogen and anti-inflammatory responses to limit inflammation. In this instance, pathogen-driven IL-10 production can establish persistence.

Fig. 2.

IL-10 and the balance between apoptosis and pathogen persistence. The presence or absence of IL-10 in infected tissue dictates not only the strength of the immune response but subsequently the amount of apoptosis incurred due to inflammation. A heavily inflamed apoptotic environment is not conducive to pathogen survival; thus, some pathogens induce IL-10 via pattern recognition receptors (PRRs) to subvert the development of acute inflammation. An abundance of IL-10 in the infected tissue decreases activation-induced inflammation and apoptosis, allowing the pathogen to persist intracellularly. If IL-10 is not induced, or it is removed, the inflammation that develops is robust enough to clear the infection, but high levels of apoptosis and parenchymal damage consequently occur.