A role for lymphotoxin β receptor in host defense against Mycobacterium bovis BCG infection

Lucas, Rudolf; Tacchini‐Cottier, Fabienne; Guler, Reto; Vesin, Dominique; Jemelin, Stéphane; Olleros, Maria L.; Marchal, G; Browning, Jeffrey L.; Vassalli, Pierre; García, Irene

doi:10.1002/(sici)1521-4141(199912)29:12<4002::aid-immu4002>3.3.co;2-j

Cited by 29 publications

(40 citation statements)

References 31 publications

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“…Compared with infliximab, etanercept forms less stable complexes with membrane-bound TNF and monomeric TNF (37,38), but binds significantly with the trimeric form of soluble TNF. Unlike infliximab, etanercept also forms stable complexes with lymphotoxin ␣, which appears to be involved in the Th1 response to Mycobacterium bovis BCG infection and in spleen granuloma formation (41).…”

Section: Discussionmentioning

confidence: 99%

Tuberculosis infection in patients with rheumatoid arthritis and the effect of infliximab therapy

Wolfe¹,

Michaud²,

Anderson³

et al. 2004

Arthritis & Rheumatism

390

189

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Objective. According to the Centers for Disease Control and Prevention, the 1999 and 2000 incidence rates for tuberculosis (TB) in the US population were 6.4 and 5.8, respectively, per 100,000 persons. Recently, reports of TB following infliximab administration have raised questions regarding the rate of TB in patients with rheumatoid arthritis (RA) generally and in those treated with infliximab in clinical practice. We undertook this study to determine the baseline rate of TB in RA prior to the introduction of infliximab and to determine the rate of TB among those currently receiving infliximab.Methods. We surveyed patients with questionnaires, followed by detailed validation from medical records and physician reports. In study 1, we evaluated 10,782 RA patients in 1998-1999 prior to the widespread use of infliximab. In study 2, we evaluated 6,460 infliximab-treated patients in 2000-2002.Results. In study 1, the lifetime rate of TB was 696 per 100,000 patients (95% confidence interval [95% CI] 547-872). Of these cases, 76.8% occurred prior to the onset of RA. During the period of prospective followup, 1 case of TB developed during 16,173 patient-years of followup, yielding a rate of 6.2 cases (95% CI 1.6-34.4) per 100,000 patients. In study 2, the TB incidence rate among infliximab-treated patients was 52.5 cases (95% CI 14.3-134.4) per 100,000 patient-years of exposure. Three of the 4 cases occurred in patients with a history of TB exposure, and no cases occurred in persons with recent TB skin tests or prophylaxis. Conclusion.The rate of TB is not increased in RA patients generally. Among infliximab-treated patients, the rate is 52.5 cases (95% CI 14.3-134.4) per 100,000 patient-years of exposure. A thorough medical history regarding TB, as well as tuberculin testing and radiographic examination (if indicated), should be an essential component of anti-tumor necrosis factor therapy.

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Section: Discussionmentioning

confidence: 99%

Tuberculosis infection in patients with rheumatoid arthritis and the effect of infliximab therapy

Wolfe¹,

Michaud²,

Anderson³

et al. 2004

Arthritis & Rheumatism

390

189

View full text Add to dashboard Cite

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“…Acid phosphatase activity was determined on frozen tissue sections (cryostat sections of 5 m) of liver as previously reported (20,23,27). The method used on tissue sections was modified for quantitative detection of acid phosphatase activity on the entire organ, as previously described (27).…”

Section: Acid Phosphatase Activitymentioning

confidence: 99%

“…The method used on tissue sections was modified for quantitative detection of acid phosphatase activity on the entire organ, as previously described (27).…”

Section: Acid Phosphatase Activitymentioning

confidence: 99%

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Transmembrane TNF Induces an Efficient Cell-Mediated Immunity and Resistance toMycobacterium bovisBacillus Calmette-Guérin Infection in the Absence of Secreted TNF and Lymphotoxin-α

Olleros

Guler

Corazza

et al. 2002

The Journal of Immunology

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105

107

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The contribution of a transmembrane (Tm) form of TNF to protective immunity against Mycobacterium bovis bacillus Calmette-Guérin (BCG) was studied in transgenic (tg) mice expressing a noncleavable Tm TNF but lacking the TNF/lymphotoxin-α (LT-α) locus (Tm TNF tg mice). These mice were as resistant to BCG infection as wild-type mice, whereas TNF/LT-α−/−, TNF−/−, and LT-α−/− mice succumbed. Tm TNF tg mice developed granulomas of smaller size but at 2- to 4-fold increased frequencies compared with wild-type mice. Granulomas were mainly formed by monocytes and activated macrophages expressing Tm TNF mRNA and accumulating acid phosphatase. NO synthase 2 activation as a key macrophage bactericidal mechanism was low during the acute phase of infection in Tm TNF tg mice but was still sufficient to limit bacterial growth and increased in late infection. While infection with virulent Mycobacterium tuberculosis resulted in very rapid death of TNF/LT-α−/− mice, it also resulted in survival of Tm TNF tg mice which presented an increase in the number of CFU in spleen (5-fold) and lungs (10-fold) as compared with bacterial load of wild-type mice. In conclusion, the Tm form of TNF induces an efficient cell-mediated immunity and total resistance against BCG even in the absence of LT-α and secreted TNF. However, Tm TNF-mediated protection against virulent M. tuberculosis infection can also be efficient but not as strong as in BCG infection, in which cognate cellular interactions may play a more predominant role in providing long-term surveillance and containment of BCG-infected macrophages.

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“…The method used on tissue sections was modified and adapted for detection of acid phosphatase activity on the whole organ, as described in Lucas et al (1999).…”

Section: Determination Of Acid Phosphatase Activitymentioning

confidence: 99%

Lethal Mycobacterium Bovis Bacillus Calmette Guérin Infection in Nitric Oxide Synthase 2-Deficient Mice: Cell-Mediated Immunity Requires Nitric Oxide Synthase 2

García

Guler

Vesin

et al. 2000

Laboratory Investigation

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SUMMARY:The role of nitric oxide (NO) in Mycobacterium bovis Bacillus Calmette Gué rin (BCG) infection was investigated using nitric oxide synthase 2 (nos2)-deficient mice, because NO plays a pivotal protective role in M. tuberculosis infection. We demonstrate that nos2-deficient mice were unable to eliminate BCG and succumbed within 8 to 12 weeks to BCG infection (10 6 CFU) with cachexia and pneumonia, whereas all infected wild-type mice survived. The greatest mycobacterial loads were observed in lung and spleen. Nos2-deficient mice developed large granulomas consisting of macrophages and activated T cells and caseous necrotic lesions in spleen. The macrophages in granulomas from nos2-deficient mice had reduced acid phosphatase activities, suggesting that NO is required for macrophage activation. The absence of NOS2 affected the cytokine production of the Th1 type of immune response, except IL-18. Serum amounts of IL-12p40 were increased and IFN-␥ was decreased compared with wild-type mice. The lack of NOS2 resulted in an overproduction of TNF, observed throughout the infection period. Additionally, TNFR1 and TNFR2 shedding was altered compared with wild-type mice. Up-regulation of TNF may be compensatory for the lack of NOS2. The late neutralization of TNF by soluble TNF receptors resulted in heightened disease severity and accelerated death in nos2-deficient mice but had no effect in wild-type mice. In conclusion, the inability of nos2-deficient mice to kill M. bovis BCG resulted in an accumulation of mycobacteria with a dramatic activation of the immune system and overproduction of pro-inflammatory cytokines, which resulted in death. (Lab Invest 2000, 80:1385-1397.

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A role for lymphotoxin β receptor in host defense against Mycobacterium bovis BCG infection

Cited by 29 publications

References 31 publications

Tuberculosis infection in patients with rheumatoid arthritis and the effect of infliximab therapy

Tuberculosis infection in patients with rheumatoid arthritis and the effect of infliximab therapy

Transmembrane TNF Induces an Efficient Cell-Mediated Immunity and Resistance toMycobacterium bovisBacillus Calmette-Guérin Infection in the Absence of Secreted TNF and Lymphotoxin-α

Lethal Mycobacterium Bovis Bacillus Calmette Guérin Infection in Nitric Oxide Synthase 2-Deficient Mice: Cell-Mediated Immunity Requires Nitric Oxide Synthase 2

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