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1.
Anaerobe ; 16(2): 125-30, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19559804

RESUMO

Clostridium sordellii, an anaerobic pathogen, has recently been associated with rapidly fatal infections following medically induced abortions and injecting drug use. Patients with C. sordellii infection display few signs of inflammation such as fever, or redness and pain at the site of infection. We hypothesized that this could be due to reduced recognition of the organism by Toll-like receptors (TLRs) of the innate immune system. An ELAM-NF-kappaB luciferase reporter system in TLR-transfected HEK cells was used to measure TLR-dependent recognition of washed, heat-killed C. sordellii and other pathogenic clostridial species. Results demonstrated that all clostridia were well recognized by TLR2 alone and that responses were greatest when TLR2 was co-expressed with TLR6. Further, isolated human monocytes produced the pro-inflammatory cytokine TNFalpha and the immunoregulator IL-10 in response to C. sordellii. In addition, C. sordellii-stimulated monocytes produced 30% less TNFalpha following treatment with an anti-TLR2 blocking antibody. These data demonstrate that innate immune recognition of, and response to, cell-associated components of C. sordellii and other clostridial pathogens are mediated by TLR2 in combination with TLR6. We conclude that the characteristic absence of inflammatory signs and symptoms in C. sordellii infection is not related to inadequate immune detection of the organism, but rather is attributable to a species-specific immune system dysfunction that remains to be elucidated.


Assuntos
Infecções por Clostridium/imunologia , Infecções por Clostridium/microbiologia , Clostridium sordellii/imunologia , Receptores Toll-Like/imunologia , Bioensaio , Linhagem Celular , Infecções por Clostridium/patologia , Clostridium sordellii/isolamento & purificação , Citocinas/metabolismo , Genes Reporter , Humanos , Imunidade Inata , Luciferases/genética , Luciferases/metabolismo , Monócitos/imunologia , Monócitos/microbiologia
2.
Clin Infect Dis ; 43(11): 1436-46, 2006 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-17083018

RESUMO

Clostridium sordellii infections pose difficult clinical challenges and are usually fatal. Most commonly, these infections occur after trauma, childbirth, and routine gynecological procedures, but they have recently been associated with medically induced abortions and injection drug use. We report 2 fatal cases, one of which was associated with minor trauma, and the other of which was associated with normal childbirth, and we summarize the clinical features of 43 additional cases of reported C. sordellii infection. Of these 45 cases, 8 (18%) were associated with normal childbirth, 5 (11%) were associated with medically induced abortion, and 2 (0.4%) were associated with spontaneous abortion. The case-fatality rate was 100% in these groups. Ten (22%) of the C. sordellii infections occurred in injection drug users, and 50% of these patients died. Other cases of C. sordellii infection (in 19 patients [43%]) occurred after trauma or surgery, mostly in healthy persons, and 53% these patients died. Overall, the mortality rate was 69% (31 of 45 patients). Eighty-five percent of all patients with fatal cases died within 2-6 days of initial infection, and nearly 80% of fatal cases developed leukemoid reactions. Rapid diagnostic tests and improved treatments are needed to reduced the morbidity and mortality associated with this devastating infection.


Assuntos
Infecções por Clostridium/epidemiologia , Infecções por Clostridium/microbiologia , Clostridium sordellii , Adolescente , Adulto , Idoso de 80 Anos ou mais , Pré-Escolar , Evolução Fatal , Feminino , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Gravidez
3.
J Med Microbiol ; 55(Pt 5): 495-504, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16585634

RESUMO

Clostridium perfringens gas gangrene is a fulminant necrotizing infection in which inflammatory cells are notably absent from infected tissues but are often massed within adjacent vessels. It has been shown that C. perfringens phospholipase C (PLC) stimulates formation of large intravascular platelet/leukocyte complexes and that PLC-induced activation of platelet gpIIbIIIa plays a major role. In vivo, such aggregates contribute to microvascular thrombosis and ischaemic necrosis of tissue. However, the effects of adherent platelets on neutrophil diapedesis have not been established. The present work investigated (1) the contribution of platelet P-selectin (CD62P) to PLC-induced cellular complex formation and (2) the effects of platelet adhesion on neutrophil diapedesis. The effects of anti-gpIIbIIIa and anti-CD62P strategies on PLC-induced complex formation were measured by flow cytometry and followed by light microscopy. Both platelet gpIIbIIIa and CD62P contributed to the formation of platelet/leukocyte complexes. Specifically, gpIIbIIIa mediated the formation of large platelet/platelet aggregates that were tethered to the leukocyte principally via CD62P. Neutrophil diapedesis, quantified by a transendothelial cell migration assay and visualized by electron microscopy, was significantly reduced (>60%) by the adherence of large platelet aggregates. It was concluded that the absence of a tissue inflammatory response in C. perfringens gas gangrene is due, in part, to impaired neutrophil mobility caused by large aggregates of adherent platelets induced by PLC. Further, an adjunctive immunotherapeutic strategy targeting both gpIIbIIIa and CD62P may improve the tissue inflammatory response, prevent vascular occlusion, maintain tissue viability, and reduce the need for radical amputation in patients with clostridial gas gangrene.


Assuntos
Plaquetas/fisiologia , Clostridium perfringens/enzimologia , Neutrófilos/fisiologia , Fosfolipases Tipo C/metabolismo , Inibição de Migração Celular , Movimento Celular , Clostridium perfringens/patogenicidade , Citometria de Fluxo , Gangrena Gasosa/microbiologia , Gangrena Gasosa/patologia , Humanos , Microscopia Eletrônica , Modelos Biológicos , Selectina-P/metabolismo , Agregação Plaquetária , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo
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