Activation of the human complement alternative pathway by Listeria monocytogenes: evidence for direct binding and proteolysis of the C3 component on bacteria

Croizé, J.; Arvieux, J.; Berche, Patrick; Colomb, Maurice G.

doi:10.1128/iai.61.12.5134-5139.1993

Cited by 39 publications

(10 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The efficient capture of C3b/iC3b-coated particles in the sinusoidal lumen is likely the result of high avidity multivalent interactions between CRIg molecules concentrated at the tip of macrophage membrane extensions and multimers of C3b and iC3b on the pathogen surface. Moreover, while CR3 only binds iC3b-coated particles, CRIg binds to C3b, the first C3 cleavage product formed on serum-opsonized pathogens (Gordon et al, 1988;Croize et al, 1993). Binding to C3b in addition to iC3b ensures immediate pathogen recognition through CRIg.…”

Section: Kupffer Cells Complement and Pathogen Recognitionmentioning

confidence: 99%

Macrophage complement receptors and pathogen clearance

Campagne¹,

Wiesmann

Brown³

2007

Cellular Microbiology

266

197

View full text Add to dashboard Cite

SummaryPhagocytosis, an important mechanism of the hostdefence system and a primary function of macrophages, is facilitated by opsonization, a process by which serum components tag pathogens for recognition by neutrophils and macrophages. Complement component C3 is central to opsonization. Its first cleavage product, C3b, forms the multisubunit enzyme, C3bBb, which proteolytically cleaves additional C3 molecules on the pathogen surface. C3b is further degraded to iC3b, C3c and C3dg, products that serve as ligands for selective complement receptors on leukocytes. This receptor-ligand interaction subsequently modulates immune responses or directly targets the pathogen for clearance by phagocytosis. Although a central role for C3 in phagocytosis of certain pathogens is well accepted, the receptors orchestrating the phagocytic response have not been well characterized. The recent structures of C3 and its breakdown products have increased our insights into the molecular basis of complement activation and recognition by their receptors. Here we review the biology of macrophage receptors for C3 fragments and discuss their role in the host response to pathogens.

show abstract

Section: Kupffer Cells Complement and Pathogen Recognitionmentioning

confidence: 99%

Macrophage complement receptors and pathogen clearance

Campagne¹,

Wiesmann

Brown³

2007

Cellular Microbiology

266

197

View full text Add to dashboard Cite

show abstract

“…In previous studies we have shown that, most likely through C3bi and C1q receptors [16][17][18] , Listeria attracts and infects MDSC 10 . These MDSC are present in large numbers in patients and mice with cancer 11,19 .…”

Section: Introductionmentioning

confidence: 99%

Tumor-targeted delivery of childhood vaccine recall antigens by attenuatedListeriareduces pancreatic cancer

Selvanesan

Chandra

Quispe

et al. 2019

Preprint

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma is poorly immunogenic, and immune suppression prevents T cell activation. We developed a microbial-based immunotherapeutic concept for selective delivery of immunogenic tetanus toxoid (TT856-1313) antigen into tumor cells by attenuated Listeria monocytogenes, and reactivation of TT-specific memory T cells to kill infected tumor cells. Treatment of KPC mice with Listeria-TT resulted in TT accumulation inside tumor cells, and attraction of TT-specific CD4 and CD8 T cells.Lymph node-like structures were frequently observed in contact with pancreatic tumors of treated mice, and exhibited CD4 and CD8 T cells producing IFNg. Gemcitabine combined with Listeria-TT significantly improved migration of CD4 T cells into tumors, and enhanced perforin and granzyme B production. The combination treatment also significantly reduced pancreatic tumors and metastases in Panc-02 and KPC mouse models, with minimal side effects, turning "cold" tumors into "hot" tumors. This study provides insight into mechanisms for improving immunotherapy for pancreatic cancer.selectively attracts MDSC through the production of cytokines and factors 11,20 , where MDSC deliver Listeria to the TME as a Trojan horse 10,19 . Once at the tumor site, Listeria spreads from MDSC into tumor cells through a cell-to-cell mechanism unique to Listeria 21 . Listeria can also infect tumor cells directly 22 . Listeria would be rapidly killed in healthy tissues, but is protected from immune clearance in the TME through strong immune suppression. Because of this combination of selective attraction of MDSC by bacteria and cancer with the strong immune suppression occurring in the TME but not in normal tissues, Listeria can selectively enter, multiply, and survive in the TME but not in normal tissues 10,19,23,24 . Based on these results we now use Listeria as a platform for the selective delivery of anticancer agents to the TME 19,23,25 .In the current study, we tested the combination of Listeria-TT+GEM (Fig 1b) in two mouse models of pancreatic cancer, a syngeneic Panc-02 model 26 and a transgenic KPC model 27,28 . Listeria-TT was administered intraperitoneally, and the in vivo uptake by tumor cells was verified by intravital imaging. We demonstrate that the combination of Listeria-TT+GEM robustly reduced pancreatic cancer at early and advanced stages in both Panc-02 and KPC mouse models. Our results unveil new mechanisms of Listeria to improve immunotherapy for PDAC. RESULTS Development and characterization of Listeria-TTThe Listeria construct used to develop Listeria-TT includes pGG34 29 , a truncated non-cytolytic Listeriolysin O (LLO) fused to a non-toxic TT856-1313 fragment, and a myc sequence for detection as outlined in Fig 2a. Secretion of LLO-TT856-1313 protein into the culture medium by the bacteria was detected by western blotting (Fig 2b). Infection of Panc-02 tumor cells with Listeria-TT856-1313 resulted in the expression of TT protein in the tumor cells (Fig 2c).

show abstract

“…However, complement plays an important role in the innate immunity against gram‐positive bacteria as an opsonizing system enhancing their phagocytosis by polymorphonuclear (PMN) and macrophages [27]. It has been shown that human C3 binds on L. monocytogenes through activation of the alternative complement pathway, but the activation does not lead to the membrane attack complex mediated bacterial lysis [29]. In the present study, the inhibition of complement in serum by compstatin resulted in lower bactericidal effect against L. monocytogenes .…”

Section: Discussionmentioning

confidence: 99%

Roles of Group IIA Phospholipase A₂ and Complement in Killing of Bacteria by Acute Phase Serum

Grönroos¹,

Salonen²,

Viander³

et al. 2005

Scand J Immunol

View full text Add to dashboard Cite

The complement system is regarded as an important component of the innate defence system against invading bacteria. However, synergistic actions between the complement and the other components of innate immunity are incompletely known. Human group IIA phospholipase A 2 (hGIIA PLA 2 ) is an effective antibacterial enzyme in serum of patients with severe bacterial infections. Our aim was to investigate the significance of complement and hGIIA PLA 2 in acute phase serum. Serum samples were collected from patients with acute bacterial infections and from healthy control subjects. We prepared hGIIA PLA 2 -depleted serum by immunoadsorption and inhibited the activity of complement by a specific inhibitor, compstatin. The bactericidal effects of treated and untreated serum were compared by incubating Staphylococcus aureus and Listeria monocytogenes in the presence of serum. Acute phase serum effectively killed S. aureus and L. monocytogenes, and depletion of hGIIA PLA 2 significantly reduced the antibacterial effect. Complement had a weak bactericidal effect against L. monocytogenes. We conclude that hGIIA PLA 2 is the major antibacterial factor in human acute phase serum against the gram-positive bacteria S. aureus and L. monocytogenes, exceeding complement in efficiency.

show abstract

Activation of the human complement alternative pathway by Listeria monocytogenes: evidence for direct binding and proteolysis of the C3 component on bacteria

Cited by 39 publications

References 28 publications

Macrophage complement receptors and pathogen clearance

Macrophage complement receptors and pathogen clearance

Tumor-targeted delivery of childhood vaccine recall antigens by attenuatedListeriareduces pancreatic cancer

Roles of Group IIA Phospholipase A₂ and Complement in Killing of Bacteria by Acute Phase Serum

Contact Info

Product

Resources

About

Activation of the human complement alternative pathway by Listeria monocytogenes: evidence for direct binding and proteolysis of the C3 component on bacteria

Cited by 39 publications

References 28 publications

Macrophage complement receptors and pathogen clearance

Macrophage complement receptors and pathogen clearance

Tumor-targeted delivery of childhood vaccine recall antigens by attenuatedListeriareduces pancreatic cancer

Roles of Group IIA Phospholipase A2 and Complement in Killing of Bacteria by Acute Phase Serum

Contact Info

Product

Resources

About

Roles of Group IIA Phospholipase A₂ and Complement in Killing of Bacteria by Acute Phase Serum