A persistence of infection is a trademark of some viruses, notably HIV and hepatitis B and C viruses, and is in large part the result of an incompletely effective antiviral T cell immune response. Brooks et al. provide evidence that a familiar and important regulatory cytokine--interleukin (IL)-10--plays a key role in facilitating viral persistence. Using two strains of the mouse lymphocytic choriomeningitis virus (LCMV), one capable of establishing a persistent infection and the other not, they showed that the levels of IL-10 generated during infection with the former were significantly higher than with the rapidly cleared strain. The T cell responses in the persistently infected animals were also diminished, leading them to ask if IL-10 were directly responsible for allowing the persistence of one strain (and not the other) by dampening virus-specific T cells. Indeed, in mice lacking IL-10, the strain differences were less apparent and, as they also found using blocking antibodies for IL-10, this led to faster viral clearance and signs of improved T cell memory.
Although differential IL-10 expression might explain such effects, it will be useful to understand exactly how the two different strains of virus trigger distinct levels of IL-10 in the first place. Presumably, mechanisms that diminish immunity could influence other ongoing infections, including situations of bacterial co-infection. Although IL-10 was not itself tested in another study by Navarini et al., these authors do report that LCMV increases the susceptibility of mice to co-infection with bacteria. Rather surprisingly, the culprit in this case was the innate antiviral cytokine type I interferon, which induced apoptosis in bacteria-clearing granulocytes. -- SJS
Nat. Med. 12, 10.1038/nm1492 (2006); Proc. Natl. Acad. Sci. U.S.A. 103, 15535 (2006).
