{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:18:42Z","timestamp":1792459122219,"version":"4.5.0"},"reference-count":87,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T00:00:00Z","timestamp":1660867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Malaria is the cause of 600.000 deaths annually. However, these deaths represent only a tiny fraction of total malaria cases. Repeated natural infections with the causative agent, <jats:italic>Plasmodium<\/jats:italic> sp. parasites, induce protection from severe disease but not sterile immunity. Thus, immunity to <jats:italic>Plasmodium<\/jats:italic> is incomplete. Conversely, immunization with attenuated sporozoite stage parasites can induce sterile immunity albeit after multiple vaccinations. These different outcomes are likely to be influenced strongly by the innate immune response to different stages of the parasite lifecycle. Even small numbers of sporozoites can induce a robust proinflammatory type I interferon response, which is believed to be driven by the sensing of parasite RNA. Moreover, induction of innate like gamma-delta cells contributes to the development of adaptive immune responses. Conversely, while blood stage parasites can induce a strong proinflammatory response, regulatory mechanisms are also triggered. In agreement with this, intact parasites are relatively weakly sensed by innate immune cells, but isolated parasite molecules, notably DNA and RNA can induce strong responses. Thus, the innate response to <jats:italic>Plasmodium<\/jats:italic> parasite likely represents a trade-off between strong pro-inflammatory responses that may potentiate immunity and regulatory processes that protect the host from cytokine storms that can induce life threatening illness.<\/jats:p>","DOI":"10.3389\/fimmu.2022.914598","type":"journal-article","created":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T07:03:59Z","timestamp":1660892639000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":41,"title":["Innate immunity to malaria: The good, the bad and the unknown"],"prefix":"10.3389","volume":"13","author":[{"given":"Kai","family":"Pohl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian A.","family":"Cockburn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,19]]},"reference":[{"key":"B1","volume-title":"World malaria report 2021","year":"2021"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1586\/eri.13.45","article-title":"The silent threat: asymptomatic parasitemia and malaria transmission","volume":"11","author":"Lindblade","year":"2013","journal-title":"Expert Rev Anti Infect Ther"},{"key":"B3","doi-asserted-by":"publisher","first-page":"17050","DOI":"10.1038\/nrdp.2017.50","article-title":"Malaria","volume":"3","author":"Phillips","year":"2017","journal-title":"Nat Rev Dis Primer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.07.055","article-title":"Malaria: Biology and disease","volume":"167","author":"Cowman","year":"2016","journal-title":"Cell"},{"key":"B5","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1146\/annurev.micro.091208.073403","article-title":"Malaria parasite development in the mosquito and infection of the mammalian host","volume":"63","author":"Aly","year":"2009","journal-title":"Annu Rev Microbiol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0020204","article-title":"Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2","volume":"2","author":"Dondorp","year":"2005","journal-title":"PloS Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.594653","article-title":"Naturally acquired humoral immunity against plasmodium falciparum malaria","volume":"11","author":"Gonzales","year":"2020","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.63838","article-title":"Inducible mechanisms of disease tolerance provide an alternative strategy of acquired immunity to malaria","volume":"10","author":"Nahrendorf","year":"","journal-title":"eLife"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1086\/339409","article-title":"Protection of humans against malaria by immunization with radiation-attenuated plasmodium falciparum sporozoites","volume":"185","author":"Hoffman","year":"2002","journal-title":"J Infect Dis"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2518","DOI":"10.1038\/s41467-021-22740-w","article-title":"Heterologous protection against malaria by a simple chemoattenuated PfSPZ vaccine regimen in a randomized trial","volume":"12","author":"Sulyok","year":"2021","journal-title":"Nat Commun"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad9099","article-title":"Complete attenuation of genetically engineered plasmodium falciparum sporozoites in human subjects","volume":"9","author":"Kublin","year":"2017","journal-title":"Sci Transl Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.2307\/3276987","article-title":"Protective immunity produced by the injection of X-irradiated sporozoites of plasmodium berghei. 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