AUTHOR=Shu Xiang , Nie Zheng , Luo Wanxin , Zheng Yaxin , Han Zhen , Zhang Hongyan , Xia Yingjun , Deng Han , Li Fangjie , Wang Sen , Zhao Junlong , He Lan 

TITLE=Babesia microti Infection Inhibits Melanoma Growth by Activating Macrophages in Mice

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.862894

DOI=10.3389/fmicb.2022.862894

ISSN=1664-302X

ABSTRACT=<p><italic>Babesia microti</italic> is an obligate intraerythrocytic protozoan transmitted by <italic>an Ixodes</italic> tick. Infections caused by protozoa, including <italic>Plasmodium yoelii</italic> and <italic>Toxoplasma gondii</italic>, are shown to inhibit tumor development by activating immune responses. Th1 immune response and macrophages not only are essential key factors in <italic>Babesia</italic> infection control but also play an important role in regulating tumor development. In this study, we investigated the effects of <italic>B. microti</italic> infection on melanoma in tumor-bearing mice. The results showed that <italic>B. microti</italic> infection could inhibit the growth of melanoma, significantly enlarge the spleen size (<italic>p</italic> ≤ 0.0001), and increase the survival period (over 7 days) of tumor-bearing mice. Mouse spleen immune cell analysis revealed that <italic>B. microti</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 <italic>B. microti</italic> infection could inhibit tumor angiogenesis (<italic>p</italic> ≤ 0.0032). Meanwhile, both <italic>B. microti</italic>-infected erythrocytes and culture supernatant were observed to significantly (<italic>p</italic> ≤ 0.0021) induce the mRNA expression of iNOS, IL-6, and TNF-α in macrophages. Moreover, <italic>B. microti</italic> culture supernatant could also repolarize IL-4-induced M2 macrophages to the M1 type. Overall, <italic>B. microti</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.</p>