Researchers discover why salmonella is so dangerous for people with HIV

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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.

Glossary

simian immunodeficiency virus (SIV)

An HIV-like virus that can infect monkeys and apes and can cause a disease similar to AIDS. Because HIV and simian immunodeficiency virus (SIV) are closely related viruses, researchers study SIV as a way to learn more about HIV. However, SIV cannot infect humans, and HIV cannot infect monkeys. 

T helper cells

T cells that alert the immune system to produce cytotoxic T lymphocytes against a specific infection. T helper cells are also known as CD4 cells.

 

lymphocyte

A type of white blood cell that is important in the immune system. Includes B cells (B lymphocytes, which produce circulating antibodies) and T cells (T lymphocytes, which are responsible for cell-mediated immunity).

diarrhoea

Abnormal bowel movements, characterised by loose, watery or frequent stools, three or more times a day.

cytokines

Chemical "messengers" exchanged between immune cells that affect the function of the immune system. Interleukins such as IL-2 are a particular type of cytokine.

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 diarrhoea. 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 (TH17) in the walls of the ileum – the final section of the small intestine. CD4+ cells are another type of T helper lymphocyte.

TH17 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 TH17 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 TH17 response led to dissemination of Salmonella from the gut to the peripheral blood.”

The data suggest TH17 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 TH17 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.

References

Raffatellu M et al. Simian immunodeficiency virus–induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nature Medicine, published online, 23rd March 2008.