The protozoan parasite Toxoplasma gondii enters hosts through the intestinal mucosa and colonizes distant tissues such as the brain, where its progeny persists for a lifetime. We investigated the role of CD11c-and CD11b-expressing leukocytes in T gondii transport during the early step of parasitism from the mouse small intestine and during subsequent parasite localization in the brain. Following intragastric inoculation of cystcontaining parasites in mice, CD11c ؉ dendritic cells from the intestinal lamina propria, the Peyer patches, and the mesenteric lymph nodes were parasitized while in the blood, parasites were associated with the CD11c ؊ CD11b ؉ monocytes. Using adoptive transfer experiments, we demonstrated that these parasitized cells triggered a parasitic process in the brain of naive recipient mice. Ex vivo analysis of parasitized leukocytes showed that single tachyzoites remained at the cell periphery, often surrounded by the host cell plasma membrane, but did not divide. Using either a dye that labels circulating leukocytes or an antibody known to prevent CD11b ؉ circulating leukocytes from leaving the microvascular bed lumen, and chimeric mice in which the hematopoietic cells expressed the green fluorescent protein, we established that T gondii zoites hijacked CD11b ؉ leukocytes to reach the brain extravascular space. IntroductionMany microorganisms initiate interactions with vertebrate hosts through digestive mucosa. Some will develop only in these peripheral host tissues, whereas others, including the protozoan parasite Toxoplasma gondii, disseminate throughout the host organism and colonize distant nonmucosal tissues. When hosts, including humans, ingest T gondii-containing cysts or oocysts, free T gondii zoites are released in the gut lumen. They subsequently enter enterocytes, where they multiply and initiate the parasitic process per se. [1][2][3] Enterocytes loaded with zoites secrete chemokines such as monocyte chemotactic protein 1 (MCP-1/CCL-2), macrophage inflammatory protein 1␣, and ␤ (MIP-1␣ and ␤/CCL3 and CCL4), as well as MIP-2/CXCL2, 4,5 which recruit leukocytes in the lamina propria (LP) extravascular space. Parasites then disseminate to several distant tissues, including the brain, a major site supporting T gondii progeny latency. 6,7 Such features have important clinical implications since T gondii can remain, for a lifetime, cryptic as bradyzoite, a slowly replicative intracellular stage under the control of unique host-dependent immune signals. However, upon rupture of this equilibrium, such as the one occurring in HIV-loaded individuals or following tissue transplantation and cancer therapy, bradyzoites can differentiate into tachyzoites, which massively replicate. This process of parasite reactivation is assessed by pathology, especially severe to fatal cerebral toxoplasmosis. 8,9 To date, whether they are acting at the cell lineage or tissue levels, the mechanisms underlying T gondii dissemination and entry into the brain remain largely unknown.T gondii zoites display unique ...

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