Defects of monocyte interleukin 12 production and humoral immunity in Whipple's disease

Marth, Thomas; Neurath, Markus F.; Cuccherini, Brenda A.; Strober, Warren

doi:10.1053/gast.1997.v113.pm9247462

Cited by 124 publications

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“…The expression of the gene encoding IL-12p35 was down-modulated in M and in Mo. This finding was consistent with previous reports in which the low production of IL-12 by Mo was associated with WD (14). Decreased IL-12 production may prevent the development of Th1 immune response and favor the shift toward Th2 response (31).…”

Section: Discussionsupporting

confidence: 91%

“…The chronic evolution of WD evokes long-term persistence of T. whipplei in M, which requires the inhibition of M microbicidal competence. Although impaired microbicidal activity in M (13) and cell-mediated immunity, including defective production of IL-12 and IFN-␥ (14), have been reported, the nature of immune impairment leading to T. whipplei persistence is still not known. In this study, we showed that T. whipplei organisms replicated in M but were killed by Mo from healthy individuals.…”

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confidence: 99%

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IL-16 Is Critical for Tropheryma whipplei Replication in Whipple’s Disease

Desnues

Raoult

Mège

2005

The Journal of Immunology

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Whipple’s disease (WD) is a rare systemic disease caused by Tropheryma whipplei. We showed that T. whipplei was eliminated by human monocytes but replicated in monocyte-derived macrophages (Mφ) by inducing an original activation program. Two different host molecules were found to be key elements for this specific pattern. Thioredoxin, through its overexpression in infected monocytes, was involved in bacterial killing because adding thioredoxin to infected Mφ inhibited bacterial replication. IL-16, which was up-regulated in Mφ, enabled T. whipplei to replicate in monocytes and increased bacterial replication in Mφ. In addition, anti-IL-16 Abs abolished T. whipplei replication in Mφ. IL-16 down-modulated the expression of thioredoxin and up-regulated that of IL-16 and proapoptotic genes. In patients with WD, T. whipplei replication was higher than in healthy subjects and was related to high levels of circulating IL-16. Both events were corrected in patients who successfully responded to antibiotics treatment. This role of IL-16 was not reported previously and gives an insight into the understanding of WD pathophysiology.

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Section: Discussionsupporting

confidence: 91%

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confidence: 99%

IL-16 Is Critical for Tropheryma whipplei Replication in Whipple’s Disease

Desnues

Raoult

Mège

2005

The Journal of Immunology

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“…Other antibiotics such as rifampicin and chloramphenicol have proven useful in allergics, for example, to betalactams and sulfamides. Immunotherapy with gamma interferon has been used in cases refractory to antibiotic treatment (100,101).…”

Section: Discussionmentioning

confidence: 99%

“…Otros antibióticos que han sido útiles en algunos pacientes (con alergia a betalactámicos y sulfamidas, por ejemplo) son rifampicina y cloramfenicol. En los casos refractarios al tratamiento se ha utilizado inmunoterapia con gamma-interferón (100,101).…”

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Whipple's disease in Spain: a clinical review of 91 patients diagnosed between 1947 and 2001

Ojeda

Cosme²,

Lapaza

et al. 2010

Rev. esp. enferm. dig.

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Background: to determine the epidemiological, clinical, diagnostic and therapeutic characteristics of Whipple's disease in Spain.Patients and method: cases of Whipple's disease reported in the Spanish literature between 1947 and 2001 which meet histological or PCR criteria are reviewed.Results: 91 cases were included, 87.5% of which were male. The maximum incidence was between 40 and 60 years of age (68%). There was no family clustering or susceptibility by profession or surroundings. The most common symptoms and signs were: weight loss (80%), diarrhoea (63%), adenopathies (35%), skin problems (32%), abdominal pain (27%), fever (23%), joint problems (20%) and neurological problems (16%). Arthralgias, diarrhoea and fever were noted prior to diagnosis in 58, 18 and 13% of patients, respectively. Diagnosis was histological in all cases except two, which were diagnosed by PCR. Intestinal biopsy was positive in 94%. Adenopathic biopsies (mesenteric or peripheral) were suggestive in 13% of cases, and treatment was effective in 89%. There were nine relapses, four of which were neurological, although all occurred before the introduction of cotrimoxazole.Conclusions: Whipple's disease is not uncommon, although it requires a high degree of suspicion to be diagnosed in the absence of digestive symptoms. The most common and most sensitive diagnostic method is duodenal biopsy. PCR is beginning to be introduced to confirm the diagnosis and as a therapeutic control. Initial antibiotic treatment with drugs that cross the blood-brain barrier, such as cotrimoxazole and ceftriaxone, is key to achieving a cure and avoiding relapses.

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“…Apparently, the Th1 reactivity in the periphery and the intestinal mucosa is impaired (14). Low serum concentrations of IL-12p40, a reduced production of IL-12 in monocytes (15,16), and the presence of M2/alternatively activated macrophages that favor the development of Th2 responses in the intestine (17) may explain these impaired Th1 cell functions. Despite reduced Th1 activity, general immunocompetence seems to be unaffected, as no systemic opportunistic infections have been reported in Whipple's disease patients.…”

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Reduced Peripheral and MucosalTropheryma whipplei-Specific Th1 Response in Patients with Whipple’s Disease

Moos

Kunkel

Marth

et al. 2006

The Journal of Immunology

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Whipple’s disease is a rare infectious disorder caused by Tropheryma whipplei. Major symptoms are arthropathy, weight loss, and diarrhea, but the CNS and other organs may be affected, too. The incidence of Whipple’s disease is very low despite the ubiquitous presence of T. whipplei in the environment. Therefore, it has been suggested that host factors indicated by immune deficiencies are responsible for the development of Whipple’s disease. However, T. whipplei-specific T cell responses could not be studied until now, because cultivation of the bacteria was established only recently. Thus, the availability of T. whipplei Twist-MarseilleT has enabled the first analysis of T. whipplei-specific reactivity of CD4+ T cells. A robust T. whipplei-specific CD4+ Th1 reactivity and activation (expression of CD154) was detected in peripheral and duodenal lymphocytes of all healthy (16 young, 27 age-matched, 11 triathletes) and disease controls (17 patients with tuberculosis) tested. However, 32 Whipple’s disease patients showed reduced or absent T. whipplei-specific Th1 responses, whereas their capacity to react to other common Ags like tetanus toxoid, tuberculin, actinomycetes, Giardia lamblia, or CMV was not reduced compared with controls. Hence, we conclude that an insufficient T. whipplei-specific Th1 response may be responsible for an impaired immunological clearance of T. whipplei in Whipple’s disease patients and may contribute to the fatal natural course of the disease.

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Defects of monocyte interleukin 12 production and humoral immunity in Whipple's disease

Cited by 124 publications

References 0 publications

IL-16 Is Critical for Tropheryma whipplei Replication in Whipple’s Disease

IL-16 Is Critical for Tropheryma whipplei Replication in Whipple’s Disease

Whipple's disease in Spain: a clinical review of 91 patients diagnosed between 1947 and 2001

Reduced Peripheral and MucosalTropheryma whipplei-Specific Th1 Response in Patients with Whipple’s Disease

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