scholarly journals Effect of Complement Component C3 Deficiency on Experimental Lyme Borreliosis in Mice

2003 ◽  
Vol 71 (8) ◽  
pp. 4432-4440 ◽  
Author(s):  
Matthew B. Lawrenz ◽  
R. Mark Wooten ◽  
James F. Zachary ◽  
Scott M. Drouin ◽  
Janis J. Weis ◽  
...  
Keyword(s):  
Lyme Borreliosis ◽  
Early Time ◽  
Heart Tissue ◽  
Complement Component ◽  
Joint Tissue ◽  
Complement Component C3 ◽  
In The Wild ◽  
Spirochete Load ◽  
The Complement System

ABSTRACT Mice deficient in complement component C3 (C3−/−) and syngeneic C57BL/6 control mice were challenged with Borrelia burgdorferi to determine the role of complement in immune clearance and joint histopathology during experimental Lyme borreliosis. Tibiotarsal joint, ear, and heart tissues were monitored for spirochete numbers at 2, 4, 8, and 12 weeks postinoculation with 105 B. burgdorferi B31 clone 5A4 by using quantitative real-time PCR. The spirochete load in joint and ear tissue remained higher in the C3−/− mice than in the wild-type counterparts throughout the 12-week study, whereas the numbers in heart tissue of both groups of mice decreased substantially at 8 to 12 weeks postinfection. Histopathology scores for joint tissue were generally higher in the C3−/− mice compared to C57BL/6 controls at 2 and 4 weeks postinfection, which may reflect the presence of higher numbers of bacteria in the joints at these early time points. Levels of anti-B. burgdorferi immunoglobulin G tended to be reduced in the C3−/− mice compared to control mice. Furthermore, a 5.5-fold-lower number of the complement-sensitive Borrelia garinii was needed to infect C3−/− mice compared to C57BL/6 mice, indicating that its sensitivity to complement is one barrier to infection of the mouse model by B. garinii. These results indicate that the complement system may be important in controlling the early dissemination and progression of B. burgdorferi infection.

scholarly journals Infection of Interleukin 17 Receptor A-Deficient C3H Mice with Borrelia burgdorferi Does Not Affect Their Development of Lyme Arthritis and Carditis

2015 ◽  
Vol 83 (7) ◽  
pp. 2882-2888 ◽  
Author(s):  
Carrie E. Lasky ◽  
Kara E. Jamison ◽  
Darcie R. Sidelinger ◽  
Carmela L. Pratt ◽  
Guoquan Zhang ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Lyme Borreliosis ◽  
Heart Tissue ◽  
Lyme Arthritis ◽  
Mouse Strains ◽  
Interleukin 17 ◽  
Content Type ◽  
C3h Mice ◽  
A Subunit

Recently, a number of studies have reported the presence of interleukin 17 (IL-17) in patients with Lyme disease, and several murine studies have suggested a role for this cytokine in the development of Lyme arthritis. However, the role of IL-17 has not been studied using the experimental Lyme borreliosis model of infection of C3H mice withBorrelia burgdorferi. In the current study, we investigated the role of IL-17 in the development of experimental Lyme borreliosis by infecting C3H mice devoid of the common IL-17 receptor A subunit (IL-17RA) and thus deficient in most IL-17 signaling. Infection of both C3H and C3H IL-17RA−/−mice led to the production of high levels of IL-17 in the serum, low levels in the heart tissue, and no detectable IL-17 in the joint tissue. The development and severity of arthritis and carditis in the C3H IL-17RA−/−mice were similar to what was seen in wild-type C3H mice. In addition, development of antiborrelia antibodies and clearance of spirochetes from tissues were similar for the two mouse strains. These results demonstrate a limited role for IL-17 signaling through IL-17RA in the development of disease following infection of C3H mice withB. burgdorferi.

scholarly journals The Inflammatory Feed-Forward Loop Triggered by the Complement Component C3 as a Potential Target in Endometriosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Chiara Agostinis ◽  
Sonia Zorzet ◽  
Andrea Balduit ◽  
Gabriella Zito ◽  
Alessandro Mangogna ◽  
...  
Keyword(s):  
Complement System ◽  
Immune Escape ◽  
Immune Surveillance ◽  
Complement Component ◽  
Wild Type ◽  
Local Synthesis ◽  
Knock Out ◽  
Complement Component C3 ◽  
Knock Out Mice ◽  
The Complement System

The complement system is a major component of humoral innate immunity, acting as a first line of defense against microbes via opsonization and lysis of pathogens. However, novel roles of the complement system in inflammatory and immunological processes, including in cancer, are emerging. Endometriosis (EM), a benign disease characterized by ectopic endometrial implants, shows certain unique features of cancer, such as the capacity to invade surrounding tissues, and in severe cases, metastatic properties. A defective immune surveillance against autologous tissue deposited in the peritoneal cavity allows immune escape for endometriotic lesions. There is evidence that the glandular epithelial cells found in endometriotic implants produce and secrete the complement component C3. Here, we show, using immunofluorescence and RT-qPCR, the presence of locally synthesized C3 in the ectopic endometriotic tissue, but not in the eutopic tissue. We generated a murine model of EM via injection of minced uterine tissue from a donor mouse into the peritoneum of recipient mice. The wild type mice showed greater amount of cyst formation in the peritoneum compared to C3 knock-out mice. Peritoneal washings from the wild type mice with EM showed more degranulated mast cells compared to C3 knock-out mice, consistent with higher C3a levels in the peritoneal fluid of EM patients. We provide evidence that C3a participates in an auto-amplifying loop leading to mast cell infiltration and activation, which is pathogenic in EM. Thus, C3 can be considered a marker of EM and its local synthesis can promote the engraftment of the endometriotic cysts.

scholarly journals Role of Complement in Mycobacterium avium Pathogenesis: In Vivo and In Vitro Analyses of the Host Response to Infection in the Absence of Complement Component C3

2001 ◽  
Vol 69 (12) ◽  
pp. 7729-7735 ◽  
Author(s):  
Suzanne S. Bohlson ◽  
Jennifer A. Strasser ◽  
Jacquelyn J. Bower ◽  
Jeffrey S. Schorey
Keyword(s):  
Mycobacterium Avium ◽  
Infection Process ◽  
Complement Component ◽  
Mouse Bone Marrow ◽  
Invasion Mechanisms ◽  
Complement Component C3 ◽  
Deficient Mice

ABSTRACT We investigated the importance of the host complement system in the pathogenesis of disease mediated by the intramacrophage pathogenMycobacterium avium. Mycobacteria opsonized with complement are efficiently ingested by macrophages through various complement receptors. Furthermore, unlike other bacteria, mycobacteria can activate both the alternative and classical complement pathways in the absence of specific antibodies. Therefore, to examine the role of complement in the mycobacterial infection process in vivo, mice deficient in complement component C3 were infected with M. avium. Surprisingly, C3-deficient mice infected intravenously with M. avium displayed no difference in bacterial burden or granulomatous response compared to wild-type control mice. C3-sufficient mice and C3-deficient mice were equally susceptible to infection by M. avium regardless of the genotype at thebcg locus, a locus known to confer susceptibility to infection with intracellular pathogens. In vitro studies using mouse bone marrow-derived macrophages resulted in significant M. avium invasion of macrophages in the absence of C3; however, the kinetics of infection were delayed compared to complement-mediated invasion. The data indicate that complement does not play an essential role in mediating M. avium infections in the mouse and suggest either that other invasion mechanisms can compensate for the absence of complement-mediated entry or that complement is not a major mycobacterial opsonin in vivo.

Complement depletion with humanised cobra venom factor: Efficacy in preclinical models of vascular diseases

2015 ◽  
Vol 113 (03) ◽  
pp. 548-552 ◽  
Author(s):  
David Fritzinger ◽  
Brian Gorsuch ◽  
Gregory Stahl ◽  
Carl-Wilhelm Vogel
Keyword(s):  
Tissue Injury ◽  
Vascular Diseases ◽  
Complement Component ◽  
Cobra Venom ◽  
Venom Component ◽  
Cobra Venom Factor ◽  
Pharmacological Agents ◽  
Functional Homology ◽  
Complement Component C3 ◽  
The Complement System

SummaryThe complement system is an intrinsic part of the immune system and has important functions in both innate and adaptive immunity. On the other hand, inadvertent or misdirected complement activation is also involved in the pathogenesis of many diseases, contributing solely or significantly to tissue injury and disease development. Multiple approaches to develop pharmacological agents to inhibit complement are currently being pursued. We have developed a conceptually different approach of not inhibiting but depleting complement, based on the complement-depleting activities of cobra venom factor (CVF), a non-toxic cobra venom component with structural and functional homology to complement component C3. We developed a humanised version of CVF by creating human complement component C3 derivatives with complement-depleting activities of CVF (humanised CVF) as a promising therapeutic agent for diseases with complement pathogenesis. Here we review the beneficial therapeutic effect of humanised CVF in several murine models of vascular diseases such as reperfusion injury.

scholarly journals Gamma subunit of complement component 8 is a neuroinflammation inhibitor

Brain ◽  
2020 ◽  
Author(s):  
Jong-Heon Kim ◽  
Ruqayya Afridi ◽  
Jin Han ◽  
Hyun-Gug Jung ◽  
Seung-Chan Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurological Diseases ◽  
Complement Component ◽  
Complement Components ◽  
Gamma Subunit ◽  
Small Proteins ◽  
Sphingosine 1 Phosphate ◽  
The Complement System

Abstract The complement system is part of the innate immune system that comprises several small proteins activated by sequential cleavages. The majority of these complement components, such as components 3a (C3a) and C5a, are chemotactic and pro-inflammatory. However, in this study, we revealed an inhibitory role of complement component 8 gamma (C8G) in neuroinflammation. In patients with Alzheimer's disease, who exhibit strong neuroinflammation, we found higher C8G levels in brain tissue, CSF, and plasma. Our novel findings also showed that the expression level of C8G increases in the inflamed mouse brain, and that C8G is mainly localized to brain astrocytes. Experiments using recombinant C8G protein and shRNA-mediated knockdown showed that C8G inhibits glial hyperactivation, neuroinflammation, and cognitive decline in acute and chronic animal models of Alzheimer’s disease. Additionally, we identified sphingosine-1-phosphate receptor 2 (S1PR2) as a novel interaction protein of C8G and demonstrated that astrocyte-derived C8G interacts with S1PR2 to antagonize the pro-inflammatory action of S1P in microglia. Taken together, our results reveal the previously unrecognized role of C8G as a neuroinflammation inhibitor. Our findings pave the way towards therapeutic containment of neuroinflammation in Alzheimer’s disease and related neurological diseases.

scholarly journals Immunolocalization of the complement component C1q in the mucous membrane of the human duodenum (duodenitis II-III degree)

2019 ◽  
pp. 71-74
Author(s):  
T. S. Zamolodchikova ◽  
B. B. Shoibonov ◽  
E. V. Svirshchevskaya
Keyword(s):  
Intestinal Epithelium ◽  
Basolateral Membrane ◽  
Barrier Properties ◽  
Complement Component ◽  
Cathepsin G ◽  
Duodenal Glands ◽  
Cell Adhesion Proteins ◽  
The Complement System ◽  
Secretory Ducts

In order to establish the supposed role of the complement system in the regulation of homeostasis and defense reactions in the intestinal epithelium, an immunofluorescent analysis was conducted of localizing the C1q complement component in the inflamed mucosa of the human duodenum (DM) (duodenitis II-III degree) using C1q-specific antibodies. The findings suggest a pronounced presence of the C1q complement component in various DM areas during inflammation, both in the epithelial layer and in the lamina propria, where C1q is localized in the region of the basolateral membrane of enterocytes and some free cells, presumably neutrophils, macrophages and mast cells. A C1q-specific reaction in the epithelial cells and secretory ducts of the duodenal glands indicates a possible secretion of C1q. Co-localization of C1q, cathepsin G and cell adhesion proteins in the DM epithelium implies their interaction in the regulation of tissue metabolism, modification and maintenance of the barrier properties of the intestinal epithelium in normal and with inflammation.

scholarly journals Important roles of C5a and C5aR in tumor development and cancer treatment

2019 ◽  
Vol 136 ◽  
pp. 06012
Author(s):  
Wang Yuxuan
Keyword(s):  
Complement System ◽  
Tumor Therapy ◽  
Tumor Development ◽  
Tumor Formation ◽  
Complement Component ◽  
Innate Defense ◽  
And Migration ◽  
And Control ◽  
The Complement System

The complement system is part of the body's innate defense immune system, which can identify and eliminate invasive pathogenic microorganisms to maintain normal life activities. Complement Component 5a (C5a) is an active anaphylatoxin produced after complement system activation, closely related to tumor formation. C5a is highly expressed in a variety of tumors, and combines with its Complement Component 5a Receptor (C5aR) to increase the proliferation and migration of tumor cells. This review will comprehensively elaborate the important role of C5a/C5aR in the process of tumor genesis and development from the three aspects of signal transduction pathways related to tumor, C5a/C5aR and tumor formation, and C5a/C5aR inhibitors and tumor therapy. Finally, the principle of complement inhibition is used to inhibit tumor metastasis, reduce the rate of tumor diffusion, and control the trend of tumor deterioration.

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