Type I IFNs are immune molecules that have a central role in antiviral host defense. They have been shown to be of clinical benefit in the treatment of a number of viral infections and cancers, and molecules such as Poly-ICLC that potently induce long-lived type I IFN responses are in clinical trials. However, data generated by Lis Antonelli and colleagues, at the National Institutes of Health, Bethesda, indicate that Poly-ICLC exacerbates lung damage and bacterial load in mice infected with the bacterium that causes tuberculosis, Mycobacterium tuberculosis, leading them to suggest that such agents should be used with caution in individuals in which M. tuberculosis is dormant.
In the study, the marked increase in lung bacterial load and widespread lung damage observed in Poly-ICLC–treated M. tuberculosis–infected mice, which was absent in mice lacking the receptor for type I IFNs, was accompanied by a dramatic increase in the number of myeloid immune cells characterized as CD11b+F4/80+Gr1int in the lungs. These cells, which were recruited to the lungs by the chemoattractant CCL2 induced by Poly-ICLC, preferentially supported bacterial growth, providing a mechanistic explanation as to why Poly-ICLC exacerbates lung damage and bacterial load in M. tuberculosis–infected mice.
TITLE: Intranasal Poly-IC treatment exacerbates tuberculosis in mice through the pulmonary recruitment of a pathogen-permissive monocyte/macrophage population
AUTHOR CONTACT:
Lis R.V. Antonelli
Centro de Pesquisas René Rachou – FIOCRUZ, Minas Gerais, Brazil.
Phone: 55.31.3379.7766; Fax: 55.31.3349.7835; E-mail: lisantonelli@cpqrr.fiocruz.br.
View this article at: http://www.jci.org/articles/view/40817?key=81fba50158c3ecb117a8
Journal
Journal of Clinical Investigation