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During mouse lung infection, complement factor C3 and the anaphylatoxin C3a augment protection against <jats:italic>C. psittaci<\/jats:italic> by a so far unknown mechanism. To clarify how complement contributes to the early, innate and the late, specific immune response and resulting protection, this study addresses the amount of C3, the timing when its presence is required as well as the anaphylatoxin receptor(s) mediating its effects and the complement-dependent migration of dendritic cells. Challenge experiments with <jats:italic>C. psittaci<\/jats:italic> on various complement KO mice were combined with transient decomplementation by pharmacological treatment, as well as the analysis of <jats:italic>in vivo<\/jats:italic> dendritic cells migration. Our findings reveal that a plasma concentration of C3 close to wildtype levels was required to achieve full protection. The diminished levels of C3 of heterozygote C3<jats:sup>+\/\u2212<\/jats:sup> mice permitted already relative effective protection and improved survival as compared to C3<jats:sup>\u2212\/\u2212<\/jats:sup> mice, but overall recovery of these animals was delayed. Complement was in particular required during the first days of infection. However, additionally, it seems to support protection at later stages. Migration of CD103<jats:sup>+<\/jats:sup> dendritic cells from the infected lung to the draining lymph node\u2014as prerequisite of antigen presentation\u2014depended on C3 and C3aR and\/or C5aR. Our results provide unique mechanistic insight in various aspects of complement-dependent immune responses under almost identical, rather physiological experimental conditions. Our study contributes to an improved understanding of the role of complement, and C3a in particular, in infections by intracellular bacteria.<\/jats:p>","DOI":"10.3389\/fimmu.2021.580594","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T13:47:11Z","timestamp":1615297631000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Complement and Chlamydia psittaci: Early Complement-Dependent Events Are Important for DC Migration and Protection During Mouse Lung Infection"],"prefix":"10.3389","volume":"12","author":[{"given":"Martin","family":"Kohn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Lanfermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Laudeley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silke","family":"Glage","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Rheinheimer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Klos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/nrmicro.2016.30","article-title":"Chlamydia cell biology and pathogenesis","volume":"14","author":"Elwell","year":"2016","journal-title":"Nat Rev Microbiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.vetmic.2008.09.046","article-title":"Chlamydophila psittaci infections in birds: a review with emphasis on zoonotic consequences","volume":"135","author":"Harkinezhad","year":"2009","journal-title":"Vet Microbiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/microorganisms7050146","article-title":"Chlamydiaceae: diseases in primary hosts and zoonosis","volume":"7","author":"Cheong","year":"2019","journal-title":"Microorganisms."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1111\/j.1469-0691.2011.03604.x","article-title":"Intracellular bacteria and adverse pregnancy outcomes","volume":"17","author":"Baud","year":"2011","journal-title":"Clin Microbiol Infect."},{"key":"B5","doi-asserted-by":"publisher","first-page":"97","DOI":"10.4103\/ijo.IJO_870_16","article-title":"Chlamydial eye infections: current perspectives","volume":"65","author":"Satpathy","year":"2017","journal-title":"Indian J Ophthalmol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1183\/09031936.00.16510010","article-title":"Chlamydia pneumoniae and the lung","volume":"16","author":"Hammerschlag","year":"2000","journal-title":"Eur Respir J."},{"key":"B7","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.vetmic.2008.09.048","article-title":"Chlamydial infections in duck farms associated with human cases of psittacosis in France","volume":"135","author":"Laroucau","year":"2009","journal-title":"Vet Microbiol."},{"key":"B8","unstructured":"Compendium of measures to control Chlamydia psittaci infection among humans (psittacosis) and pet birds (avian chlamydiosis), 2000. 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