Salmonella & HIV

Adam Legge writing for Aidsmap (March 25, 2008)

Researchers discover why salmonella is so dangerous for people with HIV

Researchers believe they have discovered why people with HIV are far more likely to die of Salmonella food poisoning, compared to those without HIV who tend to suffer a bout of diarrhoea.

Their study, published online in Nature Medicine, suggests the virus disrupts the normal gastrointestinal lining, allowing the Salmonella bacteria to cross into the bloodstream causing death.

The rise in numbers of people with AIDS in sub-Saharan Africa has been associated with a big increase in cases of what is termed nontyphoidal Salmonella serotype (NTS) infections.

NTS are a common cause of food-borne diseases across the world but tend to be confined to the intestine, usually causing a week-long bout of diarrhea. But up to half of HIV-infected African people die after contracting NTS infection.

Now, US and UK researchers have looked at NTS infection in rhesus macaque monkeys infected with simian immunodeficiency virus (SIV), which is similar to HIV.

They have found that SIV infection leads to a depletion in the numbers of a type of lymphocyte called T helper type 17 (T^H17) in the walls of the ileum – the final section of the small intestine. CD4+ cells are another type of T helper lymphocyte.

T^H17 cells produce a cytokine – or chemical messenger – called interleukin 17 (IL-17) which plays a pivotal role in the gut’s response to infection.

It is this reduction in IL-17 which is thought to allow the gut wall to become ‘leaky’, allowing the NTS bacteria to cross into and infect the bloodstream.

One of the researchers, Professor Satya Dandekar, chair of the department of medical microbiology and immunology at the University of California at Davis said: “We found that animals that had no SIV infection were able to generate immediate responses to bacterial exposure, producing T^H17 cells in large amounts.”

But the SIV-infected animals had either a significantly lower response or failed to produce measurable amounts of the cytokine, he said. “This muted T^H17 response led to dissemination of Salmonella from the gut to the peripheral blood.”

The data suggest T^H17 may be a useful biomarker for monitoring HIV infection and testing the efficacy of vaccines and other therapies. The authors also suggest that efforts to enhance T^H17 function could improve existing antiretroviral treatments.

But the research also has wider implications, with this interruption in the gut’s immune response possibly explaining how HIV can maintain reservoirs of infection that evade drug treatment.

Reference

Simian immunodeficiency virus–induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut.
Manuela Raffatellu et al
Nature Medicine, published online, 23^rd March 2008. | doi:10.1038/nm1743

Link to Nature Medicine abstract

Link to Aidsmap report