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

Authors

Sean P. Riley, Vector-borne Disease Laboratories, Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA sriley@lsu.edu.
Abigail I. Fish, Vector-borne Disease Laboratories, Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA.
Fabio Del Piero, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA.
Juan J. Martinez, Vector-borne Disease Laboratories, Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA.

Document Type

Article

Publication Date

6-1-2018

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 and that genetic ablation of complement increases susceptibility to infection. Interaction of with serum-borne complement leads to activation of the complement cascade, producing three effector mechanisms that could negatively influence 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 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-γ) 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.

Publication Source (Journal or Book title)

Infection and immunity

Recommended Citation

Riley, S. P., Fish, A. I., Del Piero, F., & Martinez, J. J. (2018). Immunity against the Obligate Intracellular Bacterial Pathogen Rickettsia australis Requires a Functional Complement System. Infection and immunity, 86 (6) https://doi.org/10.1128/IAI.00139-18