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Oral infection with Toxoplasma gondii results in dysbiosis and enteritis, both of which revert to normal during chronic infection. However, whether infection leaves a lasting impact on mucosal responses remains uncertain. Here we examined the effect of the chemical irritant dextran sodium sulfate (DSS) on intestinal damage and wound healing in chronically infected mice. Our findings indicate that prior infection with T. gondii exacerbates damage to the colon caused by DSS and impairs wound healing by suppressing stem cell regeneration of the epithelium. Enhanced tissue damage was attributable to inflammatory monocytes that emerge preactivated from bone marrow, migrate to the intestine, and release inflammatory mediators, including nitric oxide. Tissue damage was reversed by neutralization of inflammatory monocytes or nitric oxide, revealing a causal mechanism for tissue damage. Our findings suggest that chronic infection with T. gondii enhances monocyte activation to increase inflammation associated with a secondary environmental insult., Competing Interests: The authors declare no competing interest.

Microneme (MIC) proteins play important roles in the recognition, adhesion, and invasion of host cells by Toxoplasma gondii Previous studies have shown that MIC proteins are highly immunogenic in the mouse and recognized by human serum antibodies. Here we report that T. gondii antigens MIC1, MIC3, MIC4, and MIC6 were capable of inducing memory responses leading to production of gamma interferon (IFN-γ) by T cells from T. gondii -infected mice. Production of IFN-γ was demonstrated using enzyme-linked immunosorbent spot (ELISPOT) assay and also intracellular cytokine staining. All four MIC antigens displayed very high sensitivity (100%) and specificity (86 to 100%) for detecting chronic infection. Interestingly, IFN-γ was produced by both CD4 + and CD8 + T cells in BALB/c mice but primarily by CD4 + T cells in C57BL/6 mice. Phenotypic characterization of IFN-γ-producing CD4 + and CD8 + T cells in BALB/c mice and CD4 + T cells in C57BL/6 mice revealed effector memory T cells (CD44 hi CD62L lo ) as the predominant cells that contributed to IFN-γ production in response to MIC antigens. Effector memory responses were seen in mice of different major histocompatibility complex class II (MHC-II) haplotypes, suggesting that MIC antigens contain epitopes that are broadly recognized. IMPORTANCE Current diagnosis of toxoplasmosis relies almost exclusively on antibody detection, and while detection of IgG provides a useful estimate of prior infection, it does not alone indicate immune status. In contrast, detection of IFN-γ responses to T. gondii antigens has been used to monitor immune responsiveness in HIV-infected patients, thus providing valuable predictions about the potential for disease reactivation. However, specific T. gondii antigens that can be used in assays to detect cellular immunity remain largely undefined. In this study, we examined the diagnostic potential of microneme antigens of T. gondii using IFN-γ detection assays. Our findings demonstrate that MIC antigens (MIC1, MIC3, MIC4, and MIC6) elicit IFN-γ responses from memory T cells in chronically infected mice. Monitoring IFN-γ production by T cells stimulated with MIC antigens provided high sensitivity and specificity for detection of T. gondii infection in mice. Taken together, these studies suggest that microneme antigens might be useful as an adjunct to serological testing to monitor immune status during infection., (Copyright © 2019 Saraav et al.)