How genes guide our response to pathogens

Have you ever wondered why some healthy people cannot defend themselves well against bacteria or fungi while others may get away with mild symptomsIJ Researchers, including one of Indian-origin, believe that genetic factors that control the immune cell response to pathogens could partly explain this varied response.

The team investigated the response of immune cells from 200 healthy volunteers when stimulated with a comprehensive list of pathogens outside the human body, and has correlated these responses with four million genetic variants (SNPs). 

The study was performed by scientists from University Medical Centre Groningen, Radboud University Medical Centre (both in the Netherlands) and Harvard Medical School (Boston, US). 

"We all encounter pathogens on a daily basis, but we don't all defend ourselves against bacteria or fungi, for example, in the same way. Some people experience mild symptoms, others may become violently ill or even die,” said Vinod Kumar, Assistant Professor of functional genomics and infectious diseases at University Medical Centre Groningen (UMCG).

"We wanted to discover how much individual genetic differences determine this variable response,” Kumar, who is one of the senior authors of the study, said.

The study, published in the journal Nature Medicine, focused on the role of cytokines, small peptides used by immune cells as signals to guide their response to an infectious agent. 

"We observed large differences in cytokine production between individuals,” explained Kumar.

"Their responses were also specific to the different pathogens,” Kumar noted.

This suggests that cytokines contribute to the varied responses to pathogens, and that each infection triggers a specific cytokine response pathway. Previous studies on unstimulated immune cells had shown little variation between individuals.

The next step was to investigate if the responses were under genetic control.

They identified six genomic regions that influence cytokine responses, suggesting that cytokine production is at least partly genetically determined.