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Thus, it is possible for individuals to experience concomitant infection with helminth and intracellular microbes. Although the helminth-induced type 2 response can suppress type 1 proinflammatory responses required for the immunity against intracellular pathogens in the context of a coinfection, conflicting evidence suggest that helminth infection can enhance antimicrobial immunity. Using a coinfection model with the intestinal helminth Heligmosomoides polygyrus followed by infection with Toxoplasma gondii in Mus Musculus, we showed that the complex and dynamic effect of helminth infection is highly suppressive during the innate phase (days 0\u20133) of T. gondii infection and less stringent during the acute phase (d10). Helminth coinfection had a strong suppressive effect on the neutrophil, monocytic, and early IFN-\u03b3\/IL-12 responses. The IFN-\u03b3 response was later restored by compensatory production from T cells despite decreased effector differentiation of T. gondii\u2013specific CD8 T cells. In accordance with the attenuated IFN-\u03b3 response, parasite loads were elevated during the acute phase (d10) of T. gondii infection but were transiently controlled by the compensatory T cell response. Unexpectedly, 40% of helminth-coinfected mice exhibited a sustained weight loss phenotype during the postacute phase (d14\u201318) that was not associated with T. gondii outgrowth, indicating that coinfection led to decreased disease tolerance during T. gondii infection. Our work uncovers the dynamic nature of the helminth immunomodulatory effects on concomitant infections or immune responses and unveils a loss of disease tolerance phenotype triggered by coinfection with intestinal helminth.<\/jats:p>","DOI":"10.4049\/jimmunol.2200504","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T05:03:04Z","timestamp":1672722184000},"page":"2160-2171","source":"Crossref","is-referenced-by-count":9,"title":["The Impact of Helminth Coinfection on Innate and Adaptive Immune Resistance and Disease Tolerance during Toxoplasmosis"],"prefix":"10.1093","volume":"209","author":[{"given":"Eliezer","family":"Rovira-Diaz","sequence":"first","affiliation":[{"name":"Department of Medicine and Center for Immunity and Inflammation, New Jersey Medical School, Rutgers University , Newark, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5505-3933","authenticated-orcid":false,"given":"Darine W","family":"El-Naccache","sequence":"additional","affiliation":[{"name":"Department of Medicine and Center for Immunity and Inflammation, New Jersey Medical School, Rutgers University , Newark, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jojo","family":"Reyes","sequence":"additional","affiliation":[{"name":"Department of Medicine and Center for Immunity and Inflammation, New Jersey Medical School, Rutgers University , Newark, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0278-7543","authenticated-orcid":false,"given":"Yanlin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medicine and Center for Immunity and Inflammation, New Jersey Medical School, Rutgers University , Newark, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2709-285X","authenticated-orcid":false,"given":"Azadeh","family":"Nasuhidehnavi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Center for Immunity and Inflammation, New Jersey Medical School, Rutgers University , Newark, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8314-8785","authenticated-orcid":false,"given":"Fei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine and Center for Immunity and Inflammation, New Jersey Medical School, Rutgers University , Newark, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William C","family":"Gause","sequence":"additional","affiliation":[{"name":"Department of Medicine and Center for Immunity and Inflammation, New Jersey Medical School, Rutgers University , Newark, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4814-8445","authenticated-orcid":false,"given":"George S","family":"Yap","sequence":"additional","affiliation":[{"name":"Department of Medicine and Center for Immunity and Inflammation, New Jersey Medical School, Rutgers University , Newark, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"2025021008433963700_r1","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.jaci.2016.07.007","article-title":"Regulation of the host immune system by helminth parasites","volume":"138","author":"Maizels","year":"2016","journal-title":"J. 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