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Chlamydial infection: the link with ocular adnexal lymphomas

Nature Reviews Clinical Oncology volume 6, pages 658–669 (2009)Cite this article

A Correction to this article was published on 01 December 2009

Abstract

Chlamydiae are obligate intracellular bacteria that grow in eukaryotic cells and cause a wide spectrum of diseases. They can establish persistent infections, are mitogenic in vitro, promote polyclonal cell proliferation in vivo and induce resistance to apoptosis in infected cells—properties that might contribute to tumorigenesis. In fact, Chlamydophila psittaci (Cp) has been linked to the development and maintenance of ocular adnexal marginal zone B-cell lymphoma (OAMZL). In this indolent malignancy, Cp is transported by monocytes and macrophages and causes both local and systemic infection. Cp elementary bodies are viable and infectious in the conjunctiva and peripheral blood of patients with OAMZL. Bacterial eradication with antibiotic therapy is often followed by lymphoma regression. Despite recent advances in the understanding of this bacterium–lymphoma association, several questions remain unanswered. For instance, prevalence variations among different geographical areas and related diagnostic and therapeutic implications remain a major investigational issue. We will focus on clinical and therapeutic implications of chlamydial infections in patients with lymphomas and summarize the current knowledge on the association between Cp infection and OAMZL. Available data on the epidemiology, biology and pathogenesis of this association are analyzed and new investigative and clinical approaches are discussed.

Key Points

  • Chlamydophila psittaci (Cp) is the etiological agent of psittacosis in humans, a zoonotic disease caused by exposure to infected animals, mostly birds; Cp can also infect domestic mammals, including pets

  • A potential oncogenic role is suggested for chlamydiae based on several peculiar biological properties that imply an antigen selection process during lymphoma development

  • Cp infection prevalence varies among patients with ocular adnexal marginal zone B-cell lymphoma (OAMZL) from different geographical areas; OAMZL is usually indolent with a favorable prognosis

  • Cp is present in monocytes and macrophages that infiltrate OAMZL as demonstrated by PCR-based techniques, immunohistochemistry, immunofluorescence and direct electron microscopy

  • Cp is viable and infectious in the conjunctiva and peripheral blood of patients with OAMZL and is the first obligate intracellular bacterium to be linked with lymphomas

  • Cp eradication with doxycycline results in the removal of critical antigen stimulation and lymphoma regression in 50% of patients with OAMZL

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Figure 1: Electron microscopy of Chlamydophila psittaci in lymphoma.
Figure 2: Host cell invasion and intracellular growth of chlamydiae.
Figure 3: Immunohistochemistry of OAMZL tissue.
Figure 4: Chlamydial inclusions in J774A.1 cells.
Figure 5: A therapeutic strategy for patients with OAMZL.
Figure 6: CT scans of a patient with OAMZL.

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Acknowledgements

This work was supported in part by grants from the European Community (FP6 VITAL, Contract 037874), the Italian Ministry of Health, Alleanza Contro il Cancro—ISS (ACC-4), the Italian Association for Cancer Research (AIRC). The authors appreciate the excellent technical assistance of M. G. Cangi and L. Pecciarini from the Pathology Unit of the San Raffaele Scientific Institute, Milan, Italy; E. Pasini and S. Bergamin of the Cancer Bio-Immunotherapy Unit, IRCCS National Cancer Institute, Aviano, Italy; N. Vicari, S. Vigo and I. Labalestra of the Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Pavia, Italy, and the helpful suggestions of C. Bandi (DIPAV, Sezione di Patologia Generale e Parassitologia, Università degli Studi di Milano, Milan, Italy). We are indebted to M. Guidoboni (Cancer Bio-Immunotherapy Unit, IRCCS National Cancer Institute, Aviano, Italy), A. Giordano Resti (Ophthalmology Unit, San Raffaele Scientific Institute, Milan, Italy), M. M. D'Elios (Department of Internal Medicine, University of Florence, Italy), L. Politi (Neuroradiology Unit, San Raffaele Scientific Institute, Milan, Italy), L. Sacchi (Department of Animal Biology, University of Pavia, Pavia, Italy), and P. Ghia (Lab of Lymphoid Malignancies, San Raffaele Scientific Institute, Milan, Italy) for their sustained scientific collaboration.

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Authors and Affiliations

  1. Unit of Lymphoid Malignancies, San Raffaele Scientific Institute, Milan, Italy

    Andrés J. M. Ferreri, Claudio Doglioni & Maurilio Ponzoni

  2. Department of Medical Oncology, Cancer Bio-Immunotherapy Unit, Centro di Riferimento Oncologico, IRCCS National Cancer Institute, Aviano, Italy

    Riccardo Dolcetti

  3. National Reference Laboratory for Animal Chlamydioses, Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Pavia, Italy

    Simone Magnino

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  1. Andrés J. M. Ferreri
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  2. Riccardo Dolcetti
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Correspondence to Andrés J. M. Ferreri.

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Ferreri, A., Dolcetti, R., Magnino, S. et al. Chlamydial infection: the link with ocular adnexal lymphomas. Nat Rev Clin Oncol 6, 658–669 (2009). https://doi.org/10.1038/nrclinonc.2009.147

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