Innate, adaptive, and cell-autonomous immunity against Toxoplasma gondii infection

Abstract

Hosts have been fighting pathogens throughout the evolution of all infectious diseases. Toxoplasma gondii is one of the most common infectious agents in humans but causes only opportunistic infection in healthy individuals. Similar to antimicrobial immunity against other organisms, the immune response against T. gondii activates innate immunity and in turn induces acquired immune responses. After activation of acquired immunity, host immune cells robustly produce the proinflammatory cytokine interferon-γ (IFN-γ), which activates a set of IFN-γ-inducible proteins, including GTPases. IFN-inducible GTPases are essential for cell-autonomous immunity and are specialized for effective clearance and growth inhibition of T. gondii by accumulating in parasitophorous vacuole membranes. Recent studies suggest that the cell-autonomous immune response plays a protective role in host defense against not only T. gondii but also various intracellular bacteria. Moreover, the negative regulatory mechanisms of such strong immune responses are also important for host survival after infection. In this review, we will discuss in detail recent advances in the understanding of host defenses against T. gondii and the roles played by cell-autonomous immune responses.

Toxoplasmosis: Insights into immunity

Researchers are extensively studying immune responses to the single-celled parasite Toxoplasma gondii, which infects around one-third of humans, often harmlessly, but can cause life-threatening toxoplasmosis infections in patients with weakened immune systems. Masahiro Yamamoto and Miwa Sasai at Osaka University in Japan review recent advances in understanding the interactions between the immune system and the parasite. They consider non-specific ‘innate’ immune responses and also the ‘acquired’ responses that target specific parts of the parasite, referred to as antigens. Methods that selectively switch off genes in mice are revealing details presumed to also be relevant for humans. Significant molecules, molecular signaling pathways and immune-regulating processes are being identified. Recent studies suggest cell-autonomous immunity, the ability of host cells to defend themselves against attack, plays a significant role in fighting Toxoplasma gondii infection.