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Despite the co-endemicity of these diseases in regions with tropical and subtropical climates, our understanding of the complex interplay between <jats:italic><jats:italic>Plasmodium<\/jats:italic><\/jats:italic> spp. and <jats:italic><jats:italic>Leishmania<\/jats:italic><\/jats:italic> spp. co-infections on host immune response and resultant disease outcomes remains limited.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methodology\/Principal findings<\/jats:title>\n<jats:p>This study employs C57BL\/6 mice co-infected with <jats:italic><jats:italic>Leishmania major<\/jats:italic><\/jats:italic> and <jats:italic><jats:italic>Plasmodium berghei<\/jats:italic><\/jats:italic> ANKA, well-established models of cutaneous leishmaniasis and experimental cerebral malaria, respectively. Our findings demonstrate that an acute infection with <jats:italic><jats:italic>P. berghei<\/jats:italic><\/jats:italic> ANKA mitigates the progression of ongoing cutaneous leishmaniasis, as evidenced by a reduction in lesion size and parasite burden in the dermis of <jats:italic><jats:italic>L. major<\/jats:italic><\/jats:italic>-infected mice. Co-infection also led to elevated serum levels of TNF compared to the levels observed in mice infected with <jats:italic><jats:italic>L. major<\/jats:italic><\/jats:italic> alone, which may contribute to a more effective control of the <jats:italic><jats:italic>Leishmania<\/jats:italic><\/jats:italic> parasite. Furthermore, co-infected mice exhibited reduced recruitment of activated T cells and inflammatory monocytes to the site of <jats:italic><jats:italic>L. major<\/jats:italic><\/jats:italic> infection. As inflammatory monocytes can be exploited by <jats:italic><jats:italic>Leishmania<\/jats:italic><\/jats:italic> as host cells that support parasite replication, their reduced infiltration may limit parasite growth. This diminished cellular infiltration is likely to contribute to reduced local inflammation, thereby limiting tissue damage and resulting in smaller lesion size.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions\/Significance<\/jats:title>\n<jats:p>These findings elucidate the potential cross-regulation of immune responses in co-infections, underscoring the necessity to consider co-infecting pathogens in disease management and therapeutic strategies in endemic areas.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0013302","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T17:52:27Z","timestamp":1753725147000},"page":"e0013302","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Impact of co-infection with Plasmodium berghei ANKA in Leishmania major-parasitized mice on immune modulation and cutaneous leishmaniasis"],"prefix":"10.1371","volume":"19","author":[{"given":"Uyla","family":"Ornellas-Garcia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Freire-Antunes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"Rangel-Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina Heusner Gon\u00e7alves","family":"de Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f4nica Lucas","family":"Ribeiro-Almeida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e1udio Tadeu","family":"Daniel-Ribeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Cuervo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0297-6341","authenticated-orcid":true,"given":"Fl\u00e1via Lima","family":"Ribeiro-Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"pntd.0013302.ref001","volume-title":"Global vector control response 2017\u20132030","author":"World Health Organization","year":"2017"},{"key":"pntd.0013302.ref002","volume-title":"World Malaria Report (2023)","author":"World Health Organization"},{"issue":"6","key":"pntd.0013302.ref003","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.4049\/jimmunol.2000773","article-title":"CD8 and CD4 T cells infiltrate into the brain during Plasmodium berghei ANKA infection and form long-term resident memory","volume":"207","author":"N Ghazanfari","year":"2021","journal-title":"J Immunol"},{"key":"pntd.0013302.ref004","doi-asserted-by":"crossref","DOI":"10.3389\/fcimb.2017.00324","article-title":"Cytokines and chemokines in cerebral malaria pathogenesis","volume":"7","author":"J Dunst","year":"2017","journal-title":"Front Cell Infect Microbiol"},{"key":"pntd.0013302.ref005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2018.02016","article-title":"Cerebral malaria in mouse and man","volume":"9","author":"N Ghazanfari","year":"2018","journal-title":"Front Immunol"},{"key":"pntd.0013302.ref006","unstructured":"Jain S, Madjou S, Virrey F, Jain S, Madjou S, Virrey F. 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