<i>Borrelia burgdorferi</i>–Induced Oxidative Burst, Calcium Mobilization, and Phagocytosis of Human Neutrophils Are Complement Dependent

Suhonen, Juha; Hartiala, Kaija; Tuominen-Gustafsson, Helena; Viljanen, Matti K.

doi:10.1086/315195

Cited by 30 publications

(29 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Borrelia species incubated in vitro with serum have been shown to have divergent sensitivities to lysis by complement (7,25,49). We have further elucidated the role of complement in the host response to Borrelia infection by comparing the course of infection by B. burgdorferi B31 in mice genetically deficient in complement component C3 to that in mice with an intact complement system.…”

Section: Discussionmentioning

confidence: 99%

“…Lyme disease Borrelia organisms have varied abilities to survive in the presence of complement in vitro. In general, B. afzelii is resistant, B. burgdorferi is partially resistant, and B. garinii is sensitive to killing by complement in normal human serum (7,25,49). Alitalo et al (1) have shown that, in vitro, B. afzelii and B. burgdorferi are able to bind the host complement regulatory proteins factor H and factor Hlike protein 1.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Lawrenz¹,

Wooten

Zachary

et al. 2003

Infect Immun

View full text Add to dashboard Cite

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 10 5 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.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Lawrenz¹,

Wooten

Zachary

et al. 2003

Infect Immun

View full text Add to dashboard Cite

show abstract

“…5A and B), similar to what was observed for mouse macrophages. We also tested whether human neutrophil-like cells have a similar function, since neutrophil is another type of professional phagocyte that can avidly phagocytose B. burgdorferi (69,70). The result showed that uptake of the ospC mutant by human neutrophils was similar to that of the parental wild-type strain (Fig.…”

Section: Fig 3 the Ospc Mutant Disseminates And Colonizes F4/80mentioning

confidence: 97%

Outer Surface Protein OspC Is an Antiphagocytic Factor That Protects Borrelia burgdorferi from Phagocytosis by Macrophages

et al. 2015

View full text Add to dashboard Cite

cOuter surface protein C (OspC) is one of the major lipoproteins expressed on the surface of Borrelia burgdorferi during tick feeding and the early phase of mammalian infection. OspC is required for B. burgdorferi to establish infection in both immunocompetent and SCID mice and has been proposed to facilitate evasion of innate immune defenses. However, the exact biological function of OspC remains elusive. In this study, we showed that the ospC-deficient spirochete could not establish infection in NOD-scid IL2r␥ null mice that lack B cells, T cells, NK cells, and lytic complement. The ospC mutant also could not establish infection in anti-Ly6G-treated SCID and C3H/HeN mice (depletion of neutrophils). However, depletion of mononuclear phagocytes at the skin site of inoculation in SCID and C3H/HeN mice allowed the ospC mutant to establish infection in vivo. In phagocyte-depleted mice, the ospC mutant was able to colonize the joints and triggered neutrophilia during dissemination. Furthermore, we found that phagocytosis of green fluorescent protein (GFP)-expressing ospC mutant spirochetes by murine peritoneal macrophages and human THP-1 macrophage-like cells, but not in PMN-HL60, was significantly higher than parental wild-type B. burgdorferi strains, suggesting that OspC has an antiphagocytic property. In addition, overproduction of OspC in spirochetes also decreased the uptake of spirochetes by murine peritoneal macrophages. Together, our findings provide evidence that mononuclear phagocytes play a key role in clearance of the ospC mutant and that OspC promotes spirochetes' evasion of macrophages during early Lyme borreliosis. L yme disease, the most prevalent vector-borne illness in the United States (1), is a multisystem inflammatory disorder caused by infection with the spirochete Borrelia burgdorferi (2, 3). This spirochete is maintained in nature through a complex enzootic cycle involving Ixodes ticks and various small-mammal hosts. Humans, as accidental hosts, become infected after B. burgdorferiinfected ticks feed on them (4). Spirochetes replicate in the skin, spread locally, and induce an inflammatory response with a symptom known as erythema migrans, observed in most patients (2, 4). During disseminated infection, B. burgdorferi colonizes multiple tissues, leading to different clinical manifestations, including arthritis, myocarditis, and neurological and/or cutaneous abnormalities (2, 4). This acute, disseminated stage of human Lyme disease is largely recapitulated using inbred mouse strains which are susceptible to B. burgdorferi infection and develop carditis and subacute arthritis (5). Thus, the murine model provides a powerful tool to elucidate the role of spirochete virulence factors and host immunological responses during Lyme disease pathogenesis (4).The B. burgdorferi genome encodes a large number of surface lipoproteins, many of which are expressed during mammalian infection (4, 6, 7). One of these lipoproteins is the major outer surface protein C (OspC), whose production is induced within inf...

show abstract

“…These findings are correlated with the susceptibility of these strains to complement-dependent phagocytosis in human serum (30). Our aim in this study was to determine whether bacterial control of the alternative complement pathway might contribute to the pathogenicity of B. burgdorferi s.l.…”

mentioning

confidence: 98%

Complement Evasion byBorrelia burgdorferi: Serum-Resistant Strains Promote C3b Inactivation

et al. 2001

View full text Add to dashboard Cite

The most characteristic features of the Lyme disease pathogens, the Borrelia burgdorferi sensu lato (s.l.) group, are their ability to invade tissues and to circumvent the immune defenses of the host for extended periods of time, despite elevated levels of borrelia-specific antibodies in serum and other body fluids. Our aim in the present study was to determine whether B. burgdorferi is able to interfere with complement (C) at the level of C3 by accelerating C3b inactivation and thus to inhibit the amplification of the C cascade. Strains belonging to different genospecies (Borrelia garinii, B. burgdorferi sensu stricto, and Borrelia afzelii) were compared for their sensitivities to normal human serum and abilities to promote factor I-mediated C3b degradation. B. burgdorferi sensu stricto and B. afzelii strains were found to be serum resistant. When the spirochetes were incubated with radiolabeled C3b, factor I-mediated degradation of C3b was observed in the presence of C-resistant B. afzelii (n ‫؍‬ 3) and B. burgdorferi sensu stricto (n ‫؍‬ 1) strains but not in the presence of C-sensitive B. garinii (n ‫؍‬ 7) strains or control bacteria (Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis). Immunoblotting and radioligand binding analyses showed that the C-resistant strains had the capacity to acquire the C inhibitors factor H and factor H-like protein 1 (FHL-1) from growth medium and human serum. A novel surface protein with an apparent molecular mass of 35 kDa was found to preferentially bind to the N terminus region of factor H. Thus, the serum-resistant B. burgdorferi s.l. strains can circumvent C attack by binding the C inhibitors factor H and FHL-1 to their surfaces and promoting factor I-mediated C3b degradation.

show abstract

Borrelia burgdorferi–Induced Oxidative Burst, Calcium Mobilization, and Phagocytosis of Human Neutrophils Are Complement Dependent

Cited by 30 publications

References 25 publications

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

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

Outer Surface Protein OspC Is an Antiphagocytic Factor That Protects Borrelia burgdorferi from Phagocytosis by Macrophages

Complement Evasion byBorrelia burgdorferi: Serum-Resistant Strains Promote C3b Inactivation

Contact Info

Product

Resources

About