Viral immunity: Persistent viruses help opportunistic infections

[Guest guest]

Nature Reviews Microbiology 6, 876-877 (December 2008) |

doi:10.1038/nrmicro2040

Viral 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- [gamma] 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.

[Guest guest]

This was a good one to keep on hand as to why low natural killer cells may be a

marker for chronic viral infections.  Isn't CMV the most closely related to

HHV6?

Thanks for this...

________________________________

From: natasa778 <neno@...>

Sent: Friday, November 21, 2008 11:26:04 AM

Subject: Viral immunity: Persistent viruses help opportunistic infections

Nature Reviews Microbiology 6, 876-877 (December 2008) |

doi:10.1038/ nrmicro2040

Viral 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 oligodeoxynucleotid e 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- [gamma] 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.