{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:46:36Z","timestamp":1791585996734,"version":"4.3.4"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p><jats:italic>Babesia microti<\/jats:italic> is an obligate intraerythrocytic protozoan transmitted by <jats:italic>an Ixodes<\/jats:italic> tick. Infections caused by protozoa, including <jats:italic>Plasmodium yoelii<\/jats:italic> and <jats:italic>Toxoplasma gondii<\/jats:italic>, are shown to inhibit tumor development by activating immune responses. Th1 immune response and macrophages not only are essential key factors in <jats:italic>Babesia<\/jats:italic> infection control but also play an important role in regulating tumor development. In this study, we investigated the effects of <jats:italic>B. microti<\/jats:italic> infection on melanoma in tumor-bearing mice. The results showed that <jats:italic>B. microti<\/jats:italic> infection could inhibit the growth of melanoma, significantly enlarge the spleen size (<jats:italic>p<\/jats:italic> \u2264 0.0001), and increase the survival period (over 7 days) of tumor-bearing mice. Mouse spleen immune cell analysis revealed that <jats:italic>B. microti<\/jats:italic>-infected tumor-bearing mice could increase the number of macrophages and CD4+ T cells, as well as the proportion of CD4+ T cells and M1 macrophages in the tumor. Immunohistochemical assays showed that <jats:italic>B. microti<\/jats:italic> infection could inhibit tumor angiogenesis (<jats:italic>p<\/jats:italic> \u2264 0.0032). Meanwhile, both <jats:italic>B. microti<\/jats:italic>-infected erythrocytes and culture supernatant were observed to significantly (<jats:italic>p<\/jats:italic> \u2264 0.0021) induce the mRNA expression of iNOS, IL-6, and TNF-\u03b1 in macrophages. Moreover, <jats:italic>B. microti<\/jats:italic> culture supernatant could also repolarize IL-4-induced M2 macrophages to the M1 type. Overall, <jats:italic>B. microti<\/jats:italic> exerted antitumor effects by stimulating the immune system of tumor-bearing mice and inducing the polarization of immunosuppressive M2 macrophages to pro-inflammatory M1 macrophages.<\/jats:p>","DOI":"10.3389\/fmicb.2022.862894","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T06:38:56Z","timestamp":1655879936000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Babesia microti Infection Inhibits Melanoma Growth by Activating Macrophages in Mice"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiang","family":"Shu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Nie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanxin","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxin","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjun","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangjie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"469","DOI":"10.4049\/jimmunol.1201209","article-title":"Immune-mediated regression of established B16F10 melanoma by intratumoral injection of attenuated Toxoplasma gondii protects against rechallenge.","volume":"190","author":"Baird","year":"","journal-title":"J. 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