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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Toxoplasma gondii secretes a novel dense granule protein, GRA24, that traffics from the vacuole to the host cell nucleus where it prolongs p38a activation and correlates with proinflammatory cytokine production.

Lethal meningitis triggered by the hypervirulent group B streptococcus clone ST-17 is mediated by a novel surface protein called HvgA.

Gay et al. identify a Toxoplasma gondii secreted effector that recruits NuRD transcriptional repressor and blocks IFN-γ–stimulated STAT1-dependent gene expression, thus dampening host responses to infection.

SummaryTrypanosoma cruzi enters cells by a unique mechanism, distinct from phagocytosis. Invasion is facilitated by disruption of host cell actin microfilaments, and involves recruitment and fusion of host lysosomes at the site of parasite entry. These findings implied the existence of transmembrane signaling mechanisms triggered by the parasites in the host cells before invasion. Here we show that infective trypomastigotes or their isolated membranes, but not the noninfective epimastigotes, induce repetitive cytosolic-free Ca 2+ transients in individual normal rat kidney fibroblasts, in a pertussis toxin-sensitive manner. Parasite entry is inhibited by buffering or depleting host cell cytosolic-free Ca 2+, or by pretreatment with Ca 2+ channel blockers or pertussis toxin. In contrast, invasion is enhanced by brief exposure of the host cells to cytochalasin D. These results indicate that a trypomastigote membrane factor triggers cytosolic-free Ca 2+ transients in host cells through a G-protein-coupled pathway. This signaling event may promote invasion through modulation of the host cell actin cytoskeleton.

Apicomplexan parasites are thought to actively invade the host cell by gliding motility. This movement is powered by the parasite's own actomyosin system, and depends on the regulated polymerisation and depolymerisation of actin to generate the force for gliding and host cell penetration. Recent studies demonstrated that Toxoplasma gondii can invade the host cell in the absence of several core components of the invasion machinery, such as the motor protein myosin A (MyoA), the microneme proteins MIC2 and AMA1 and actin, indicating the presence of alternative invasion mechanisms. Here the roles of MyoA, MLC1, GAP45 and Act1, core components of the gliding machinery, are re-dissected in detail. Although important roles of these components for gliding motility and host cell invasion are verified, mutant parasites remain invasive and do not show a block of gliding motility, suggesting that other mechanisms must be in place to enable the parasite to move and invade the host cell. A novel, hypothetical model for parasite gliding motility and invasion is presented based on osmotic forces generated in the cytosol of the parasite that are converted into motility.

During invasion, apicomplexan parasites form an intimate circumferential contact with the host cell, the tight junction (TJ), through which they actively glide. The TJ, which links the parasite motor to the host cell cytoskeleton, is thought to be composed of interacting apical membrane antigen 1 (AMA1) and rhoptry neck (RON) proteins. Here we find that, in Plasmodium berghei, while both AMA1 and RON4 are important for merozoite invasion of erythrocytes, only RON4 is required for sporozoite invasion of hepatocytes, indicating that RON4 acts independently of AMA1 in the sporozoite. Further, in the Toxoplasma gondii tachyzoite, AMA1 is dispensable for normal RON4 ring and functional TJ assembly but enhances tachyzoite apposition to the cell and internalization frequency. We propose that while the RON proteins act at the TJ, AMA1 mainly functions on the zoite surface to permit correct attachment to the cell, which may facilitate invasion depending on the zoite-cell combination.