<i>Borrelia burgdorferi</i>
            Resistance to a Major Skin Antimicrobial Peptide Is Independent of Outer Surface Lipoprotein Content

Sarkar, Amit; Tilly, Kit; Stewart, Philip E.; Bestor, Aaron; Battisti, James M.; Rosa, Patricia A.

doi:10.1128/aac.00558-09

Cited by 13 publications

(17 citation statements)

References 50 publications

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“…The data presented here are consistent with previously published evidence (25,54,57) that the presence of OspC does not alter the host innate immune response to the bacteria. Macrophages in vitro have the same survival rates when infected FIG.…”

Section: Discussionsupporting

confidence: 92%

“…It may be argued other cell types, including those of the innate immune system, may be affected by the expression of OspC, in particular with regard to the production of MCP-1, as bone marrow-derived macrophages in culture did not respond to B. burgdorferi in terms of MCP-1 production. Neutrophils are also found at the site of infection (64), and in a recent paper Sarkar and colleagues (54) investigated the possible in vitro effects on B. burgdorferi of the antimicrobial peptide cathelicidin, which is produced by neutrophils and keratinocytes and so is inducible in the skin in response to infection (6). However, there were no differences between the WT and ⌬C B. burgdorferi strains in their resistances to cathelicidin (54).…”

Section: Discussionmentioning

confidence: 99%

“…While OspC expression is maximal at the time at which the bacteria are moving from tick to mammal, expression wanes, and OspC-expressing bacteria are rapidly cleared as the adaptive immune response is activated (28,36,43,63). Previous work investigated potential roles for OspC in overcoming challenges from the mammalian innate immune system (25,54,57) and in bacterial adaptation to the mammalian environment (57). Those studies, however, found that OspC is still required for infection of SCID and MyD88-deficient mice (25,57), while ospC mutant bacteria are able to survive in dialysis membrane chambers implanted into the peritoneal cavity (57).…”

mentioning

confidence: 99%

“…Although the role of OspC in the establishment of infection and its potential role in the interaction of the bacteria with the immune system have been studied in vivo (25,36,54,57,60,61,63), the role of OspC in the interaction of the bacteria with the innate immune system specifically at the site of inoculation in the skin has not been reported. In this work, we investigated the possibility that OspC may affect the response of macrophages cultured in vitro to B. burgdorferi and then moved on to examine the role of OspC at the site of inoculation in mouse skin, which cannot be recapitulated in vitro.…”

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confidence: 99%

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Effect of Borrelia burgdorferi OspC at the Site of Inoculation in Mouse Skin

et al. 2010

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The Borrelia burgdorferi surface lipoprotein OspC is a critical virulence factor, but its precise role in the establishment of B. burgdorferi infection remains unclear. To determine whether OspC affects the host response at the site of inoculation of the bacterium, the recruitment of macrophages and neutrophils and the production of cytokines were examined at the site of infection by wild-type, ospC mutant, and complemented mutant B. burgdorferi strains. Of the 21 cytokines tested, monocyte chemoattractant protein 1 (MCP-1), keratinocyte-derived chemokine (KC, CXCL1), and vascular endothelial growth factor (VEGF) were found at increased levels at the site of inoculation of B. burgdorferi, and the levels varied with the production of OspC at one or more time points over the 1-week course of infection. The kinetics of expression and the dependence on OspC production by B. burgdorferi varied among the cytokines. The production of KC and MCP-1, and the appearance of monocytic infiltrates, correlated with the presence of the bacteria rather than with OspC specifically. In contrast, VEGF production was not correlated simply to the presence of the bacteria and is influenced by the presence of OspC. In in vitro assays, OspC and B. burgdorferi expressing OspC stimulated the growth of endothelial cells more than did the controls. These data suggest the possibility of a novel role for OspC in the life of B. burgdorferi at the interface of its mammalian and tick hosts.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Effect of Borrelia burgdorferi OspC at the Site of Inoculation in Mouse Skin

et al. 2010

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“…The ospC mutant is cleared within the first 48 h of infection in the murine host (21), suggesting a protective role of OspC against innate defenses. The OspC protective effect in spirochetes seems to be independent of the actions of major antimicrobial peptides (22). OspC also has been proposed to play roles in promoting survival and/or dissemination of spirochetes within the mammalian host.…”

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confidence: 99%

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

et al. 2015

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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...

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