Toxoplasma gondii Infection Inhibits Th17-Mediated Spontaneous Development of Arthritis in Interleukin-1 Receptor Antagonist-Deficient Mice

Washino, Takuya; Moroda, Masataka; Iwakura, Yoichiro; Aosai, Fumie

doi:10.1128/iai.05680-11

Cited by 23 publications

(15 citation statements)

References 43 publications

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“…Additionally, transcriptional analysis of Batf3 -dependent DC in the mesLN and spleen revealed a significant increase in Il12b expression in mesLN DC but not splenic DC post-infection (Figure S6L) . Although we cannot completely exclude the possibility of a transient and discrete contribution of the BM, our present results, in agreement with previous studies (Oldenhove et al, 2009; Washino et al, 2012), support the idea that the MALT is the dominant source of early IL-12 following per-oral T. gondii infection.…”

Section: Resultssupporting

confidence: 91%

Bone-Marrow-Resident NK Cells Prime Monocytes for Regulatory Function during Infection

et al. 2015

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SUMMARY Tissue-infiltrating Ly6Chi monocytes play diverse roles in immunity, ranging from pathogen killing to immune regulation. How and where this diversity of function is imposed remains poorly understood. Here we show that during acute gastrointestinal infection, priming of monocytes for regulatory function preceded systemic inflammation and was initiated prior to bone marrow egress. Notably, natural killer (NK) cell-derived IFN-γ promoted a regulatory program in monocyte progenitors during development. Early bone marrow NK cell activation was controlled by systemic interleukin-12 (IL-12) produced by Batf3-dependent dendritic cells (DC) in the mucosal-associated lymphoid tissue (MALT). This work challenges the paradigm that monocyte function is dominantly imposed by local signals following tissue recruitment, and instead proposes a sequential model of differentiation in which monocytes are pre-emptively educated during development in the bone marrow to promote their tissue-specific function.

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Section: Resultssupporting

confidence: 91%

Bone-Marrow-Resident NK Cells Prime Monocytes for Regulatory Function during Infection

et al. 2015

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“…Previously, we showed that Th1 cells are preferentially differentiated in T. gondiiinfected mice (17). In these mice, Th17 cell differentiation is suppressed, consistent with the observation that Th17 cell differentiation and Th1 cell differentiation are mutually suppressive (18).…”

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confidence: 87%

Interleukin-17A-Deficient Mice Are Highly Susceptible to Toxoplasma gondii Infection Due to Excessively Induced T. gondii HSP70 and Interferon Gamma Production

et al. 2017

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Interleukin17A (IL-17A) is known to be involved in the host defense against pathogens and the pathogenesis of autoimmune diseases. Previously, we showed that excessive amounts of interferon gamma (IFN-γ) play an important role in the pathogenesis of the lethal effects of by inducing anaphylactic responses. In the study described in this report, we examined the effects of IL-17A deficiency on murine host defense against oral infection. IL-17A-deficient C57BL/6 (B6) mice exhibited higher rates of mortality than wild-type (WT) mice during the acute phase of infection. CD4 T cells in the mesenteric lymph nodes (mLNs) and ileum of -infected IL-17A-deficient mice produced higher levels of IFN-γ than did those of WT mice. In addition, the level of HSP70 (HSP70) expression was also significantly increased in the ileum, mLNs, liver, and spleen of infected IL-17A-deficient mice compared with that in WT mice. These elevated levels of expression of HSP70 and IFN-γ in infected IL-17A-deficient mice were presumably linked to the IL-17A defect since they decreased to WT levels after treatment with recombinant IL-17A. Furthermore, IL-17A-deficient mice were highly susceptible to the anaphylactic effect ofHSP70, and the survival of IL-17A-deficient mice during the acute phase was improved by treatment with an anti-HSP70 monoclonal antibody. These results suggest that IL-17A plays an important role in host survival against infection by protecting the host from an anaphylactic reaction via the downregulation ofHSP70 and IFN-γ production.

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“…T. gondii infection may not always be deleterious. For example, it inhibits the development of arthritis in mice deficient in the interleukin receptor antagonist (IL1RN) [106]. T. gondii infection is also able to reduce infarct size in focal cerebral ischaemia in mice, an effect attributed to the ability of infection to increase the expression of nerve growth factor, as well as that of anti-inflammatory cytokines and of glutathione and oxidative stress protective genes, while reducing the expression of proinflammatory cytokines [107].…”

Section: Resultsmentioning

confidence: 99%

Toxoplasmosis and Polygenic Disease Susceptibility Genes: ExtensiveToxoplasma gondiiHost/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders

Carter

2013

Journal of Pathogens

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Toxoplasma gondii is not only implicated in schizophrenia and related disorders, but also in Alzheimer's or Parkinson's disease, cancer, cardiac myopathies, and autoimmune disorders. During its life cycle, the pathogen interacts with ~3000 host genes or proteins. Susceptibility genes for multiple sclerosis, Alzheimer's disease, schizophrenia, bipolar disorder, depression, childhood obesity, Parkinson's disease, attention deficit hyperactivity disorder (P from 8.01E − 05 (ADHD) to 1.22E − 71) (multiple sclerosis), and autism (P = 0.013), but not anorexia or chronic fatigue are highly enriched in the human arm of this interactome and 18 (ADHD) to 33% (MS) of the susceptibility genes relate to it. The signalling pathways involved in the susceptibility gene/interactome overlaps are relatively specific and relevant to each disease suggesting a means whereby susceptibility genes could orient the attentions of a single pathogen towards disruption of the specific pathways that together contribute (positively or negatively) to the endophenotypes of different diseases. Conditional protein knockdown, orchestrated by T. gondii proteins or antibodies binding to those of the host (pathogen derived autoimmunity) and metabolite exchange, may contribute to this disruption. Susceptibility genes may thus be related to the causes and influencers of disease, rather than (and as well as) to the disease itself.

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Toxoplasma gondii Infection Inhibits Th17-Mediated Spontaneous Development of Arthritis in Interleukin-1 Receptor Antagonist-Deficient Mice

Cited by 23 publications

References 43 publications

Bone-Marrow-Resident NK Cells Prime Monocytes for Regulatory Function during Infection

Bone-Marrow-Resident NK Cells Prime Monocytes for Regulatory Function during Infection

Interleukin-17A-Deficient Mice Are Highly Susceptible to Toxoplasma gondii Infection Due to Excessively Induced T. gondii HSP70 and Interferon Gamma Production

Toxoplasmosis and Polygenic Disease Susceptibility Genes: ExtensiveToxoplasma gondiiHost/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders

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