The IL-12 response of primary human DC and monocytes to Toxoplasma gondii is stimulated by phagocytosis of live parasites rather than host cell invasion

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Authors

• KW Tosh
• S Bonne-Annee
• SM Singer
• A Sher
• D Jankovic

Abstract

As a major natural host for Toxoplasma gondii, the mouse is widely used for the study of the immune response to this medically important protozoan parasite. However, murine innate recognition of toxoplasma depends on the interaction of parasite profilin with TLR11 and TLR12, two receptors that are functionally absent in humans. This raises the question of how human cells detect and respond to T. gondii. Here, we show that primary monocytes and dendritic cells from peripheral blood of healthy donors produce IL-12 and other proinflammatory cytokines when exposed to toxoplasma tachyzoites. Cell fractionation studies determined that IL-12 and TNFalpha secretion is limited to CD16+ monocytes and the CD1c+ subset of dendritic cells. In direct contrast to their murine counterparts, human myeloid cells fail to respond to soluble tachyzoite extracts and instead require contact with live parasites. Importantly, we found that tachyzoite phagocytosis, but not host cell invasion, is required for cytokine induction. Together these findings formally demonstrate an unappreciated role for phagocytosis of live parasites in the innate recognition of T. gondii by human myeloid cells. This route of pathogen sensing is distinct from that utilized by mice, possibly reflecting the more highly specialized host-parasite adaptation of the latter species.

Scientific Focus Area: Immunology

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