Migratory responses of leukocytes infected with Toxoplasma gondii

Lambert, Henrik; Dellacasa-Lindberg, Isabel; Barragán, Antonio

doi:10.1016/j.micinf.2010.10.002

Cited by 54 publications

(64 citation statements)

References 17 publications

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“…2C). In line with observations in DC and macrophages (20,21), live intracellular tachyzoites were necessary for migratory activation of microglia, while other stimuli had little or no effect (Fig. 2D).…”

Section: Resultssupporting

confidence: 89%

Migratory Activation of Primary Cortical Microglia upon Infection with Toxoplasma gondii

et al. 2011

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Disseminated toxoplasmosis in the central nervous system (CNS) is often accompanied by a lethal outcome.Studies with murine models of infection have focused on the role of systemic immunity in control of toxoplasmic encephalitis, while knowledge remains limited on the contributions of resident cells with immune functions in the CNS. In this study, the role of glial cells was addressed in the setting of recrudescent Toxoplasma infection in mice. Activated astrocytes and microglia were observed in the close vicinity of foci with replicating parasites in situ in the brain parenchyma. Toxoplasma gondii tachyzoites were allowed to infect primary microglia and astrocytes in vitro. Microglia were permissive to parasite replication, and infected microglia readily transmigrated across transwell membranes and cell monolayers. Thus, infected microglia, but not astrocytes, exhibited a hypermotility phenotype reminiscent of that recently described for infected dendritic cells. In contrast to gamma interferon-activated microglia, Toxoplasma-infected microglia did not upregulate major histocompatibility complex (MHC) class II molecules and the costimulatory molecule CD86. Yet Toxoplasma-infected microglia and astrocytes exhibited increased sensitivity to T cell-mediated killing, leading to rapid parasite transfer to effector T cells in vitro. We hypothesize that glial cells and T cells, besides their role in triggering antiparasite immunity, may also act as "Trojan horses," paradoxically facilitating dissemination of Toxoplasma within the CNS. To our knowledge, this constitutes the first report of migratory activation of a resident CNS cell by an intracellular parasite.

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Section: Resultssupporting

confidence: 89%

Migratory Activation of Primary Cortical Microglia upon Infection with Toxoplasma gondii

et al. 2011

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“…Furthermore, blood CD11b+ cells (which may include NK cells) were able to shuttle tachyzoites across the blood‐brain barrier 5, 30. However, in agreement with our findings, transfer of a mixed lymphocyte population (predominantly B cells) did not augment parasite dissemination relative to free tachyzoite controls 36. Our findings are also in agreement with more recent data demonstrating that free tachyzoites are able to cross the blood‐brain barrier without the assistance of host immune cells 8.…”

Section: Discussionsupporting

confidence: 87%

“…Contrary to DCs, the hypermotile phenotype in NK cells is observed only in tissues, and not in simplified in vitro assays 36. Therefore, while NK cell hypermotility clearly occurs in vivo during natural infections, it has been challenging to determine the mechanism underlying this hypermotile phenotype.…”

Section: Discussionmentioning

confidence: 99%

Parasitized Natural Killer cells do not facilitate the spread of Toxoplasma gondii to the brain

Petit-Jentreau

Glover

Coombes

2018

Parasite Immunology

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Summary Toxoplasma gondii is a protozoan parasite capable of invading immune cells and co‐opting their migratory pathways to disseminate through the host. Natural Killer (NK) cells can be directly invaded by the parasite and this invasion alters NK cell migration, producing a hypermotile phenotype. However, the consequences of this hypermotile phenotype for the dissemination of T. gondii to the brain remain unknown. To address this, C57BL6/J mice were infected with freshly egressed tachyzoites (type II Prugniaud strain) or with parasitized NK cells. Under both conditions, parasite loads in the brain were comparable, indicating that parasitized NK cells were not able to facilitate spread of T. gondii to the brain. Consistent with this, we found no evidence for the recruitment of endogenous NK cells to the brain at early time points post‐infection, nor any changes in the expression of α4β1 integrin, involved in recruitment of NK cells to the brain. We therefore found no evidence for a role for hypermotile NK cells in delivery of parasites to the brain during acute infection with T. gondii.

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“…This interplay could then underlie a more robust innate and adaptive immune activation, leading to effective control of avirulent parasites. Additionally, avirulent T. gondii strains preferentially infect mononuclear cells, including naive resident macrophages (this report), monocytes (29,30) and neutrophils (31), and also differentially induce hypermigratory phenotype in infected macrophages and dendritic cells (10,32). It is tempting to speculate that these maneuvers together represent a constellation of adaptive responses characteristic of avirulent T. gondii.…”

Section: Discussionmentioning

confidence: 73%

Avirulent strains of Toxoplasma gondii infect macrophages by active invasion from the phagosome

Zhao

Marple

Ferguson

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Unlike most intracellular pathogens that gain access into host cells through endocytic pathways, Toxoplasma gondii initiates infection at the cell surface by active penetration through a moving junction and subsequent formation of a parasitophorous vacuole. Here, we describe a noncanonical pathway for T. gondii infection of macrophages, in which parasites are initially internalized through phagocytosis, and then actively invade from within a phagosomal compartment to form a parasitophorous vacuole. This phagosome to vacuole invasion (PTVI) pathway may represent an intermediary link between the endocytic and the penetrative routes for host cell entry by intracellular pathogens. The PTVI pathway is preferentially used by avirulent strains of T. gondii and confers an infectious advantage over virulent strains for macrophage tropism.virulence | Trojan horse | apicomplexa | phagocytes P hagocytosis is one of the most ancient defense mechanisms for the host to destroy invasive pathogens. However, most intracellular pathogens exploit this very pathway for internalization and survival in phagocytes (1). A notable exception to this paradigm is the infection pathway used by apicomplexan parasites-exemplified by Toxoplasma gondii. The current consensus model of T. gondii infection suggests that the parasite actively invades host cells by forming a moving junction (MJ) at the host cell surface (2). Penetration of T. gondii through this junction is largely driven by its own actin motor complex (3). The parasitophorous vacuoles formed by this pathway are nonfusogenic with the host endocytic system, thus evading lysosome-mediated destruction (4-6). However, recent reports including the findings that host F-actin participates in entry by T. gondii (7), and that the parasite is still able to infect cells, albeit much less efficiently, even without some key components of the invasion machinery (8), suggest the existence of alternative infection pathways for Toxoplasma. The active penetration model was defined largely by using nonphagocytic host cells and hypervirulent strains of the parasite. Unlike their virulent counterparts, the interaction of avirulent Toxoplasma strains with macrophage and dendritic cell results in heightened innate cytokine and chemokine production (9) and the development of a "hypermotile" host cellular phenotype (10), which promotes the control of acute infection and mediates dissemination into sites of parasite latency (11,12). Here, we investigated whether avirulent parasites interact with phagocytic host cells in a fundamentally different way from the outset. We found that the avirulent Toxoplasma strains infect macrophages initially via phagocytosis and subsequent active penetration from within the phagosome to form a parasitophorous vacuole. This hybrid invasion pathway may represent an intermediary link between the endocytic and the penetrative routes for host cell entry by intracellular pathogens. ResultsTo investigate whether avirulent Toxoplasma (PTG, type II strain) uses the active penetration p...

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Migratory responses of leukocytes infected with Toxoplasma gondii

Cited by 54 publications

References 17 publications

Migratory Activation of Primary Cortical Microglia upon Infection with Toxoplasma gondii

Migratory Activation of Primary Cortical Microglia upon Infection with Toxoplasma gondii

Parasitized Natural Killer cells do not facilitate the spread of Toxoplasma gondii to the brain

Avirulent strains of Toxoplasma gondii infect macrophages by active invasion from the phagosome

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