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

Riley, Sean P.; Fish, Abigail I.; Piero, Fábio Del; Martínez, Juan José

doi:10.1128/iai.00139-18

Cited by 13 publications

(19 citation statements)

References 54 publications

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“…A previous study had shown that the complement system is required for the immune response to Rickettsia infection (Riley et al., 2018). We sought to identify the mechanism of complement activation that occurs during Rickettsia exposure, with the hypothesis that Rickettsia ‐mediated complement activation relies on the classical complement activation pathway.…”

Section: Resultsmentioning

confidence: 99%

“…C1q −/− mice lack exon 3 of the complement component 1, q subcomponent, alpha polypeptide gene leading to incomplete assembly of the C1 complex and ablation of the entire classical complement activation pathway (Fonseca et al., 2017). WT and C1q −/− mice were intravenously infected with 0.5 minimum lethal doses of R. australis strain Cutlack (Riley et al., 2018).…”

Section: Resultsmentioning

confidence: 99%

“…While complement appears to be activated in vivo, Rickettsia have been shown to be inherently resistant to complement‐mediated killing (Fish et al., 2017; Garza et al., 2017; Riley et al., 2014) (Riley et al., 2012). However, the dichotomy between Rickettsia and complement is not purely one dimensional as a recent study has shown that immunity against the pathogenic species R. australis requires a functional complement system (Riley et al., 2018). The complement proteins C3 and C9 are not deposited on the bacteria, so complement efficacy is not dependent on complement‐mediated phagocytosis nor direct killing of the bacteria.…”

Section: Introductionmentioning

confidence: 99%

“…The complement proteins C3 and C9 are not deposited on the bacteria, so complement efficacy is not dependent on complement‐mediated phagocytosis nor direct killing of the bacteria. Instead, infected C3‐knock‐out mice show a decrease in IFN‐γ production and early IgG production, suggesting that activation of complement influences the remainder of the immune system to produce anti‐ Rickettsia effectors (Riley et al., 2018). With the knowledge that complement contributes to the immune response to these obligate intracellular pathogens these questions remain: Could we modulate the complement system to enhance the efficacy of the immune response?…”

Section: Introductionmentioning

confidence: 99%

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Contribution of classical complement activation and IgM to the control of Rickettsia infection

Dahmani

Cook

Zhu

et al. 2021

Molecular Microbiology

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Pathogenic Rickettsia are obligate intracellular bacteria and the etiologic agents of many life‐threatening infectious diseases. Due to the serious nature of these infections, it is imperative to both identify the responsive immune sensory pathways and understand the associated immune mechanisms that restrict Rickettsia proliferation. Previous studies have demonstrated that the mammalian complement system is both activated during Rickettsia infection and contributes to the immune response to infection. To further define this component of the mammalian anti‐Rickettsia immune response, we sought to identify the mechanism(s) of complement activation during Rickettsia infection. We have employed a series of in vitro and in vivo models of infection to investigate the role of the classical complement activation pathway during Rickettsia infection. Depletion or elimination of complement activity demonstrates that both C1q and pre‐existing IgM contribute to complement activation; thus implicating the classical complement system in Rickettsia‐mediated complement activation. Elimination of the classical complement pathway from mice increases susceptibility to R. australis infection with both increased bacterial loads in multiple tissues and decreased immune activation markers. This study highlights the role of the classical complement pathway in immunity against Rickettsia and implicates resident Rickettsia‐responsive IgM in the response to infection.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Contribution of classical complement activation and IgM to the control of Rickettsia infection

Dahmani

Cook

Zhu

et al. 2021

Molecular Microbiology

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“…Cytotoxic T lymphocyte activities against infected host cells and complement-mediated bacterial killing modulate host-protective immune responses against rickettsial infections (Walker, Olano and Feng 2001 ; Riley et al . 2018 ). Recent studies highlight the critical roles of inflammasome and interferons in fighting against infections caused by Rickettsia (Smalley et al .…”

Section: Discussionmentioning

confidence: 99%

Virulence potential of Rickettsia amblyommatis for spotted fever pathogenesis in mice

Yen

Stern²,

Mishra

et al. 2021

Pathogens and Disease

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Rickettsia amblyommatis belongs to the spotted fever group of Rickettsia and infects Amblyomma americanum (Lone Star ticks) for transmission to offspring and mammals. Historically, the geographic range of A. americanum was restricted to the southeastern USA. However, recent tick surveys identified the progressive northward invasion of A. americanum, contributing to the increased number of patients with febrile illnesses of unknown etiology after a tick bite in the northeastern USA. While serological evidence strongly suggests that patients are infected with R. amblyommatis, the virulence potential of R. amblyommatis is not well established. Here, we performed a bioinformatic analysis of three genome sequences of R. amblyommatis and identified the presence of multiple putative virulence genes whose products are implicated for spotted fever pathogenesis. Similar to other pathogenic spotted fever rickettsiae, R. amblyommatis replicated intracellularly within the cytoplasm of tissue culture cells. Interestingly, R. amblyommatis displayed defective attachment to microvascular endothelial cells. The attachment defect and slow growth rate of R. amblyommatis required relatively high intravenous infectious doses to produce dose-dependent morbidity and mortality in C3H mice. In summary, our results corroborate clinical evidence that R. amblyommatis can cause mild disease manifestation in some patients.

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Rickettsia

Fournier¹,

Raoult²

2019

Bergey's Manual of Systematics of Archaea and Bacteria

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Rick.ett'si.a. N.L. fem. n. Rickettsia, named after Howard Taylor Ricketts, who first associated these microorganisms with spotted fever and typhus and who died of typhus contracted in the course of his studies. Proteobacteria / Alphaproteobacteria / Rickettsiales / Rickettsiaceae / Rickettsia Short , often paired rods , 0 . 3–0 . 5 μ m × 0 . 8–2 . 0 μ m . The rickettsial envelope has a typical Gram‐negative structure with a bilayer inner membrane, a peptidoglycan layer, and a bilayer outer membrane. The cells are often surrounded by a protein microcapsular layer and slime layer. Rickettsiae retain basic fuchsin when stained by Giménez method. The organisms are obligately intracellular and reside free in the cytoplasm of eukaryotic host cells , where they divide by binary fission . Rickettsiae of the spotted fever group (SFG) may also reside in the nucleus of eukaryotic host cells. Rickettsiae are closely associated with arthropods (ticks, mites, fleas, lice, and other insects) for their maintenance in nature . Their natural cycle usually involves both a vertebrate and an invertebrate host. For some, the arthropod host is both a reservoir and a vector. Transovarian transmission of the agent from the infected female to the next generation is the essential mechanism for the maintenance of many species. Rickettsial cells are usually unstable when separated from host components, except for highly stable forms found in the feces of arthropod hosts; stability can be enhanced by certain proteins, sucrose, and reagents that tend to maintain the integrity of outer membranes, osmolarity, and ATP level. Rickettsiae are best preserved by rapid freezing and storage below −50°C. The cells are rapidly inactivated at 56°C. Rickettsiae derive energy from the metabolism of glutamate via the citric acid cycle, but do not utilize glucose. They transport and metabolize phosphorylated compounds but do not synthesize or degrade nucleoside monophosphates. Rickettsial species have genomes ranging from 1.1 to 2.3 Mb. They may also have up to four plasmids. Rickettsiae are etiological agents of typhus and spotted fevers in humans . There are 31 recognized species. DNA G + C content (mol%) : 29–33. Type species : Rickettsia prowazekii da Rocha‐Lima 1916, 567. (Nom. Cons. Opin. 19, Jud. Comm. 1958, 158.)

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

Cited by 13 publications

References 54 publications

Contribution of classical complement activation and IgM to the control of Rickettsia infection

Contribution of classical complement activation and IgM to the control of Rickettsia infection

Virulence potential of Rickettsia amblyommatis for spotted fever pathogenesis in mice

Rickettsia

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