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Infection and Immunity, August 2004, p. 4480-4485, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4480-4485.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Helicobacter pylori Induces Apoptosis of Human Monocytes but Not Monocyte-Derived Dendritic Cells: Role of the cag Pathogenicity Island{dagger}

Mario Galgani,1 Immacolata Busiello,1 Stefano Censini,2 Serafino Zappacosta,1 Luigi Racioppi,1* and Raffaele Zarrilli1,3*

Dipartimento di Biologia e Patologia Cellulare e Molecolare "L. Califano",1 Dipartimento di Scienze Mediche Preventive, Università di Napoli "Federico II," Naples,3 IRIS-Chiron SpA, 53100 Siena, Italy2

Received 1 December 2003/ Returned for modification 10 March 2004/ Accepted 5 May 2004

Monocytes are circulating precursors of the dendritic cell subset, professional antigen-presenting cells with a unique ability to initiate the innate and adaptive immune response. In this study, we have investigated the effects of wild-type Helicobacter pylori strains and their isogenic mutants with mutations in known bacterial virulence factors on monocytes and monocyte-derived dendritic cells. We show that H. pylori strains induce apoptosis of human monocytes by a mechanism that is dependent on the expression of a functional cag pathogenicity island. This effect requires an intact injection organelle for direct contact between monocytes and the bacteria but also requires a still-unidentified effector that is different from VacA or CagA. The exposure of in vitro-generated monocyte-derived dendritic cells to H. pylori stimulates the release of inflammatory cytokines by a similar mechanism. Of note is that dendritic cells are resistant to H. pylori-induced apoptosis. These phenomena may play a critical role in the evasion of the immune response by H. pylori, contributing to the persistence of the infection.

* Corresponding authors. Mailing address for Luigi Racioppi: Dipartimento di Biologia e Patologia Cellulare e Molecolare "L. Califano," Università di Napoli "Federico II," Via S. Pansini n. 5, 80131 Naples, Italy. Phone: 39-081-7463359. Fax: 39-081-7463252. E-mail: racioppi{at}unina.it. Mailing address for Raffaele Zarrilli: Dipartimento di Scienze Mediche Preventive, Università di Napoli "Federico II," Via S. Pansini n. 5, 80131 Naples, Italy. Phone: 39-081-7463026. Fax: 39-081-7463352. E-mail: rafzarri{at}unina.it.

{dagger} We dedicate this study to the memory of Stelio Varrone, a mentor in science and life.

Editor: V. J. DiRita

Infection and Immunity, August 2004, p. 4480-4485, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4480-4485.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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