Effects of Clostridium difficile toxin B on human monocytes and macrophages: possible relationship with cytoskeletal rearrangement

Siffert, Jean-Claude; Baldacini, Olivier; Kuhry, Jean-Georges; Wachsmann, Dominique; Benabdelmoumene, S; Faradji, A.; Monteil, H.; Poindron, P.

doi:10.1128/iai.61.3.1082-1090.1993

Cited by 30 publications

(9 citation statements)

References 39 publications

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“…In agreement with this hypothesis, in vitro toxin A stimulated chemotaxis and chemokinesis in human granulocytes (27). Finally, toxin B enhanced the ability of gamma interferon-treated monocytes to secrete tumor necrosis factor as a probable consequence of the disorganization of the cytoskeleton (28).…”

Section: Discussionsupporting

confidence: 60%

Human antibody response to Clostridium difficile toxin A in relation to clinical course of infection

et al. 1994

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This study investigated whether differences in fecal and serum antitoxin A antibody levels may account for the duration of Clostridium difficile-associated diarrhea (CDAD) and the occurrence of relapses. By an enzyme linked-immunosorbent assay, we tested 40 patients with CDAD including 25 patients without immunodeficiency and 15 patients receiving antineoplastic drugs. Two hundred eighty serum samples and 80 normal stool samples were investigated as controls. In nonimmunocompromised patients, serum immunoglobulin (IgG) and fecal IgA antitoxin A antibody titers were significantly higher in patients who suffered a single episode (n = 21) than in those with relapsing CDAD (n = 4) whose titers were at control levels. Of these 25 patients, eight suffered from diarrhea which lasted for more than 2 weeks. These patients had significantly lower serum-and feces-specific antibody levels than the others who presented symptoms of shorter duration. In cytostatic-treated patients, antitoxin A antibody levels were similar to controls, but relapses occurred in a single case. These data suggest an association between a defective humoral response to toxin A and a more severe form of C. difficile infection. They also indicate that other host-related factors control the severity of CDAD and remain to be elucidated.

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Section: Discussionsupporting

confidence: 60%

Human antibody response to Clostridium difficile toxin A in relation to clinical course of infection

et al. 1994

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“…Recently, cell surface glycoconjugate receptors for toxin B have been demonstrated in the human colon (6) suggesting that in humans, prior insult to the epithelial barrier by toxin A is not required. Subsequently, the toxins generate local inflammation of the mucosa by inducing chemotaxis of neutrophils and inducing the release of inflammatory mediators from macrophages, neutrophils, and mast cells (24,30,31,33,38,46).…”

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confidence: 99%

Serum Antitoxin Antibodies Mediate Systemic and Mucosal Protection from Clostridium difficile Disease in Hamsters

Giannasca¹,

Zhang²,

Lei³

et al. 1999

Infect Immun

108

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Clostridium difficile is the bacterial pathogen identified as the cause of pseudomembranous colitis and is principally responsible for nosocomial antibiotic-associated diarrhea and colitis. The pathologic findings associated with this infection are believed to be caused by two large (∼300-kDa) exotoxins, toxins A and B. Because of the mucosal nature of this infection, vaccination strategies aimed at providing prophylactic or therapeutic immune protection have included immunization by mucosal routes. Using the hamster model ofC. difficile infection, we examined the protective efficacy of inactivated toxin (toxoid) vaccine formulations prepared as either culture filtrate or partially purified toxoid. We compared combination parenteral and mucosal vaccination regimens involving intranasal, intragastric, or rectal routes of immunization and found that rectal immunization in conjunction with intramuscular (i.m.) vaccination provided full protection of hamsters from death and diarrhea while the other mucosal routes did not. Protection was associated with high levels of toxin-neutralizing antibodies in serum. The requirement for adjuvants for protection was assessed by using sequential i.m. and rectal or i.m. vaccination regimens. Unexpectedly, i.m. immunization without adjuvant conferred the highest protection from death and diarrhea; this regimen elicited the highest serum anti-toxin B titers as well as toxin B neutralizing titers. Passive transfer of mouse antitoxin antibodies protected hamsters in a dose-dependent manner, demonstrating the principal role of circulating antitoxin antibodies in immunity from this toxin-mediated mucosal disease. These results suggest that prophylactic parenteral vaccination or intravenous immunotherapy could provide protection from C. difficiledisease in humans.

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“…Recently, toxin B was shown to cause necrosis in human colon tissue when biopsy specimens in Ussing chambers were exposed to the toxin (24a). Toxin B also induces the release of inflammatory mediators from human monocytes and increases cell-mediated cytotoxicity (14,40). Diarrhea and colitis result from the action of C. difficile toxins and the stimulation of local inflammation.…”

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confidence: 99%

Evaluation of formalin-inactivated Clostridium difficile vaccines administered by parenteral and mucosal routes of immunization in hamsters

Torres¹,

Lyerly²,

Hill³

et al. 1995

Infect Immun

104

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Clostridium difficile produces toxins that cause inflammation, necrosis, and fluid in the intestine and is the most important cause of nosocomial antibiotic-associated diarrhea and colitis. We evaluated C. difficile antigens as vaccines to protect against systemic and intestinal disease in a hamster model of clindamycin colitis. Formalin-inactivated culture filtrates from a highly toxigenic strain were administered by mucosal routes (intranasal, intragastric, and rectal) with cholera toxin as a mucosal adjuvant. A preparation of culture filtrate and killed whole cells was also tested rectally. The toxoid was also tested parenterally (subcutaneously and intraperitoneally) and by a combination of three intranasal immunizations followed by a combined intranasalintraperitoneal boost. Serum antibodies against toxins A and B and whole-cell antigen were measured by enzyme-linked immunosorbent assay, neutralization of cytotoxic activity, and bacterial agglutination. The two rectal immunization regimens induced low antibody responses and protected only 20% of hamsters against death and 0% against diarrhea. The intragastric regimen induced high antibody responses but low protection, 40% against death and 0% against diarrhea. Hamsters immunized by the intranasal, intraperitoneal, and subcutaneous routes were 100% protected against death and partially protected (40, 40, and 20%, respectively) against diarrhea. Among the latter groups, intraperitoneally immunized animals had the highest serum anticytotoxic activity and the highest agglutinating antibody responses. Hamsters immunized intranasally and revaccinated intraperitoneally were 100% protected against both death and diarrhea. Protection against death and diarrhea correlated with antibody responses to all antigens tested. The results indicate that optimal protection against C. difficile disease can be achieved with combined parenteral and mucosal immunization.

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Effects of Clostridium difficile toxin B on human monocytes and macrophages: possible relationship with cytoskeletal rearrangement

Cited by 30 publications

References 39 publications

Human antibody response to Clostridium difficile toxin A in relation to clinical course of infection

Human antibody response to Clostridium difficile toxin A in relation to clinical course of infection

Serum Antitoxin Antibodies Mediate Systemic and Mucosal Protection from Clostridium difficile Disease in Hamsters

Evaluation of formalin-inactivated Clostridium difficile vaccines administered by parenteral and mucosal routes of immunization in hamsters

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