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Immunity against the Obligate Intracellular Bacterial Pathogen Rickettsia australis Requires a Functional Complement System.

ABSTRACT: The complement system has a well-defined role in deterring blood-borne infections. 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 Rickettsia australis and that genetic ablation of complement increases susceptibility to infection. Interaction of Rickettsia australis with serum-borne complement leads to activation of the complement cascade, producing three effector mechanisms that could negatively influence R. australis. 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 Rickettsia 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-?) 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.

SUBMITTER: Riley SP

PROVIDER: S-EPMC5964522 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Immunity against the Obligate Intracellular Bacterial Pathogen Rickettsia australis Requires a Functional Complement System.

Riley Sean P SP Fish Abigail I AI Del Piero Fabio F Martinez Juan J JJ

Infection and immunity 20180522 6

The complement system has a well-defined role in deterring blood-borne infections. 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 wit ...[more]

PMID: 29581196

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Dataset Information

Immunity against the Obligate Intracellular Bacterial Pathogen Rickettsia australis Requires a Functional Complement System.

Publications

Immunity against the Obligate Intracellular Bacterial Pathogen Rickettsia australis Requires a Functional Complement System.

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