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However, complement is not entirely efficacious, as several bacterial pathogens, including some obligate intracellular pathogens, have evolved mechanisms for resistance. It is presumed that obligate intracellular bacteria evade complement attack by residing within a host cell; however, recent studies have challenged this presumption. Here, we demonstrate that the complement system is activated during infection with the obligate intracellular bacterium<jats:named-content content-type=\"genus-species\">Rickettsia australis<\/jats:named-content>and that genetic ablation of complement increases susceptibility to infection. Interaction of<jats:named-content content-type=\"genus-species\">Rickettsia australis<\/jats:named-content>with serum-borne complement leads to activation of the complement cascade, producing three effector mechanisms that could negatively influence<jats:named-content content-type=\"genus-species\">R. australis.<\/jats:named-content>The C9-dependent membrane attack complex can lead to deposition of a bacteriolytic membrane pore on the bacteria, but this system does not contribute to control of rickettsial infection. Similarly, complement receptor (CR1\/2)-dependent opsonophagocytosis may lead to engulfment and killing of the bacteria, but this system is also dispensable for immunity. Nevertheless, intact complement is essential for naturally acquired and antibody-mediated immunity to<jats:named-content content-type=\"genus-species\">Rickettsia<\/jats:named-content>infection. Comparison of infection in mice lacking the central complement protein C3 with infection in their wild-type counterparts demonstrated decreases in gamma interferon (IFN-\u03b3) production, IgG secretion, and spleen hyperplasia in animals lacking complement. The correlation between loss of secondary immune functions and loss of complement indicates that the proinflammatory signaling components of the complement system, and not membrane attack complex or opsonophagocytosis, contribute to the immune response to this pathogen.<\/jats:p>","DOI":"10.1128\/iai.00139-18","type":"journal-article","created":{"date-parts":[[2018,3,27]],"date-time":"2018-03-27T10:12:44Z","timestamp":1522145564000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["Immunity against the Obligate Intracellular Bacterial Pathogen Rickettsia australis Requires a Functional Complement System"],"prefix":"10.1128","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4384-4540","authenticated-orcid":false,"given":"Sean P.","family":"Riley","sequence":"first","affiliation":[{"name":"Vector-borne Disease Laboratories, Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA"},{"name":"Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail I.","family":"Fish","sequence":"additional","affiliation":[{"name":"Vector-borne Disease Laboratories, Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA"},{"name":"Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Del Piero","sequence":"additional","affiliation":[{"name":"Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Vector-borne Disease Laboratories, Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA"},{"name":"Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.13.102"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00262"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2012.07.016"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.25.11490"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830240304"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V83.11.3324.3324"},{"key":"e_1_3_3_8_2","first-page":"633","article-title":"Characterization of C3a anaphylatoxin receptor on guinea-pig macrophages","volume":"79","author":"Murakami Y","year":"1993","unstructured":"Murakami Y, Imamichi T, Nagasawa S. 1993. 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