Viral immunity: Persistent viruses help opportunistic infections

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Nature Reviews Microbiology 6, 876-877 (December 2008) | doi:10.1038/nrmicro2040Viral immunity: Persistent viruses help opportunists Persistent

viral infections make the host more susceptible to opportunistic

infections by decreasing the production of type I interferons (IFNs) by

plasmacytoid dendritic cells (pDCs) according to a study by Oldstone

and colleagues.Viral

infections induce a strong innate immune response that is orchestrated

by pDCs, an immature DC subset that uses pattern-recognition receptors

(including Toll-like receptors (TLRs)) to detect viral nucleic acids

and subsequently produces large amounts of type I IFNs. However, viral

infections are thought to suppress the host immune response by an

unknown mechanism.To investigate the effect of

viral infection on the pDC-mediated production of type I IFNs, the

authors infected mice with two isolates of lymphocytic choriomeningitis

virus (LCMV) that mimic acute and persistent infection, and examined

the levels of type I IFNs in the serum. Infection with both isolates

induced high levels of type I IFN secretion, which peaked 1 day after

infection and decreased 5 days later. Importantly, challenging the mice

with the TLR9 ligand CpG-containing oligodeoxynucleotide 5 days after

infection did not induce type I IFN production, which suggested that

LCMV infection suppressed the innate immune response.The

authors then examined whether LCMV infection affected the numbers and

function of pDCs. Infection with both LCMV isolates decreased the

numbers of pDCs and their secretion of type I IFNs, and this effect

lasted for up to 30 days in the mice that had been infected with the

persistent isolate of the virus. As other aspects of pDC function

(including the secretion of other cytokines and the expression of major

histocompatibility complex class II molecules) were not affected by the

infection, the authors concluded that LCMV infection specifically

interferes with the ability of pDCs to secrete type I IFNs.The

suppression of type I IFN secretion by the persistent isolate of LCMV

was in fact found to make the mice more susceptible to secondary

infections by unrelated pathogens, such as murine cytomegalovirus

(MCMV), than uninfected mice. This was the result of decreased type I

IFN production and, consequently, lower percentages of activated

natural killer (NK) cells, reduced NK-cell-derived IFN-

and decreased NK-cell-mediated cytotoxicity. Importantly, the mice that

had been infected with the persistent isolate of LCMV were less able to

contain the spread of the secondary MCMV infection than the control

mice.Although suppression of type I IFN production

might have different effects on different secondary infections

depending on the opportunistic pathogen, the authors clearly show that

LCMV infection can suppress the mouse immune system by interfering with

the ability of pDCs to secrete type I IFNs. This altered innate immune

response could subsequently also affect the induction of the adaptive

immune response.