Contribution of classical complement activation and IgM to the control of <i>Rickettsia</i> infection

Dahmani, Mustapha; Cook, Jack H.; Zhu, Jinyi; Riley, Sean P.

doi:10.1111/mmi.14839

Cited by 7 publications

(6 citation statements)

References 80 publications

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“…The methods by which the activity of the complement system is measured are similar to those used in the determination of cytokines. Enumerated methods include ELISA and ELISPOT immunological methods, real-time PCR, or the determination of activity and concentration of individual complement components [ 150 ].…”

Section: Diagnostics Of the Inflammatory Process In Admentioning

confidence: 99%

Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review

Twarowski

Herbet

2023

IJMS

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Alzheimer’s disease is one of the most commonly diagnosed cases of senile dementia in the world. It is an incurable process, most often leading to death. This disease is multifactorial, and one factor of this is inflammation. Numerous mediators secreted by inflammatory cells can cause neuronal degeneration. Neuritis may coexist with other mechanisms of Alzheimer’s disease, contributing to disease progression, and may also directly underlie AD. Although much has been established about the inflammatory processes in the pathogenesis of AD, many aspects remain unexplained. The work is devoted in particular to the pathomechanism of inflammation and its role in diagnosis and treatment. An in-depth and detailed understanding of the pathomechanism of neuroinflammation in Alzheimer’s disease may help in the development of diagnostic methods for early diagnosis and may contribute to the development of new therapeutic strategies for the disease.

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Section: Diagnostics Of the Inflammatory Process In Admentioning

confidence: 99%

Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review

Twarowski

Herbet

2023

IJMS

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“…In this case, the pathomechanisms may relate to a delayed IgG class switch, altered T-cell response, and altered cytokine levels ( 114 ). Similarly, the pathogen burden in various organs during infections with Rickettsia , yet another intracellular pathogen transmitted among others by ticks, was significantly increased in C1qKO mice ( 115 ).…”

Section: Resultsmentioning

confidence: 99%

C1q as a target molecule to treat human disease: What do mouse studies teach us?

Schulz

Trendelenburg

2022

Front. Immunol.

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The complement system is a field of growing interest for pharmacological intervention. Complement protein C1q, the pattern recognition molecule at the start of the classical pathway of the complement cascade, is a versatile molecule with additional non-canonical actions affecting numerous cellular processes. Based on observations made in patients with hereditary C1q deficiency, C1q is protective against systemic autoimmunity and bacterial infections. Accordingly, C1q deficient mice reproduce this phenotype with susceptibility to autoimmunity and infections. At the same time, beneficial effects of C1q deficiency on disease entities such as neurodegenerative diseases have also been described in murine disease models. This systematic review provides an overview of all currently available literature on the C1q knockout mouse in disease models to identify potential target diseases for treatment strategies focusing on C1q, and discusses potential side-effects when depleting and/or inhibiting C1q.

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“…The anaphylatoxin receptors therefore join an ever-increasing repertoire of innate immune receptors that can indirectly or directly sense the presence of Rickettsia bacilli. Previous findings have demonstrated that the innate immune system can directly detect Rickettsia through preexisting IgM molecules that activate the complement system to produce anaphylatoxins ( 91 ). Therefore, the pathway from (i) IgM recognition of the bacterial surface, (ii) anaphylatoxin production, and (iii) anaphylatoxin receptor agonism is a strong surveillance pathway for alerting mammalian cells about the presence of Rickettsia .…”

Section: Discussionmentioning

confidence: 99%

“…C3a and C5a concentrations were determined by an enzyme-linked immunosorbent assay as previously described ( 91 ). Appropriate media were harvested on day 3 and used for the evaluation of complement activation.…”

Section: Methodsmentioning

confidence: 99%

Anaphylatoxin signaling activates macrophages to control intracellular Rickettsia proliferation

Dahmani,

Zhu,

Cook

et al. 2023

Microbiol Spectr

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Pathogenic Rickettsia species proliferate within the cytoplasm of permissive host cells in vivo . The cytoplasm of these host cells is adequate to support the complex metabolic and physiological needs for Rickettsia growth. However, a dramatic host/pathogen interplay occurs when Rickettsia encounter innate immune cells, whereby the bacteria can proliferate as normal or the host can restrict bacterial growth. This interplay is most divergent within myeloid host cells, where intra- and extracellular factors can produce either successful Rickettsia parasitism or innate immune control of bacterial proliferation. With the prior knowledge that the mammalian complement system is activated during mammalian infection, we sought to determine if extracellular complement activation and anaphylatoxin signaling can modify the fate of Rickettsia within mononuclear host cells. Results indicate that supplementation of growth media with either C3a or C5a anaphylatoxin peptides is sufficient for many myeloid cells to control the proliferation of multiple different Rickettsia species. Chemical or genetic disruption of anaphylatoxin signaling or anaphylatoxin receptors eliminates complement-induced restriction of bacterial proliferation. Finally, anaphylatoxin signaling modifies macrophage physiology by inducing inflammatory phenotypes that ultimately control the intracellular proliferation of these pathogens. IMPORTANCE Pathogenic Rickettsia species are extremely dangerous bacteria that grow within the cytoplasm of host mammalian cells. In most cases, these bacteria are able to overpower the host cell and grow within the protected environment of the cytoplasm. However, a dramatic conflict occurs when Rickettsia encounter innate immune cells; the bacteria can “win” by taking over the host, or the bacteria can “lose” if the host cell efficiently fights the infection. This manuscript examines how the immune complement system is able to detect the presence of Rickettsia and alert nearby cells. Byproducts of complement activation called anaphylatoxins are signals that “activate” innate immune cells to mount an aggressive defensive strategy. This study enhances our collective understanding of the innate immune reaction to intracellular bacteria and will contribute to future efforts at controlling these dangerous infections.

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

Cited by 7 publications

References 80 publications

Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review

Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review

C1q as a target molecule to treat human disease: What do mouse studies teach us?

Anaphylatoxin signaling activates macrophages to control intracellular Rickettsia proliferation

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