Size matters: immune cells mount different defences against pathogens based on size

14 September 2014

Immune cells called neutrophils sense microbe size and selectively release NETs in response to large pathogens.

Image: Immune cells called neutrophils sense microbe size and selectively release NETs in response to large pathogens.

Immune cells called neutrophils selectively deploy large web-like structures to trap and kill large pathogens such as fungi, according to new research from the Medical Research Council's National Institute for Medical Research (NIMR; now part of the Francis Crick Institute).

The findings have implications for improving treatments for patients whose immune systems are unable to effectively mount such defences to large pathogens, as well as for understanding autoimmune diseases where this method of defence goes awry and can result in damage to a patient's own body.

Dr Veni Papayannopoulos of NIMR explained: "Microbial pathogens come in different sizes. Much is known about how immune cells deal with microbes that are small enough to be taken up and killed inside cells through a process called phagocytosis. In contrast, how the immune system counters large microbes is much less clear.

"Immune cells called neutrophils are the foot soldiers of the immune system. Our study shows that they can sense microbial size and mount a strategy that captures and kills large microbes outside cells by releasing web-like structures called neutrophil extracellular traps (NETs)."

 

Dr Papayannopoulos and his team studied cell cultures of human neutrophils and microbes and performed experiments using mouse models of infection to identify the importance of the NETs for immune defence.

Previously, it was assumed that neutrophils, which were once thought to be relatively 'simple-minded' cells,  released NETs indiscriminately in response to pathogens. However this study highlights their ability to make sophisticated decisions depending on the type of infection they encounter.

Dr Papayannopoulos said: "Deficiency in neutrophil function in humans is associated with life threatening susceptibility to bacterial and fungal infections. However, the contribution of NETs in human immunity has been difficult to dissect, because most mutations in patients with weakend immune systems disrupt both NET release and phagocytic killing.

"By showing that NETs are selectively implemented to specifally fight large pathogens our study has separated the roles of these two antimicrobial strategies in immune defense and explains why human patients with specific defects in neutrophil function are susceptible to particular pathogens. We hope that these new findings will help clinicians formulate more targeted treatments for these patients. 

"On the other hand, abnormal release and insufficient clearance of NETs are implicated in a number of inflammatory and autoimmune diseases. Our experiments show that mutations that block phagocytosis disrupt the ability of neutrophils to distinguish between small and large microbes and, as a consequence, these cells misfire NETs in response to small pathogens causing unnecessary tissue damage. We hope that our work may offer new insights into the cause and treatment of such diseases."

The paper, Neutrophils sense microbe size and selectively release neutrophil extracellular traps in response to large pathogens, is published in Nature Immunology.

  • Immune cells called neutrophils selectively deploy  large web-like structures to trap and kill large pathogens such as fungi outside cells, according to a new study. In comparison, it has long been known that small pathogens are engulfed and killed inside cells using a process called phagocytosis. 
  • The research has implications for improving immune defences for patients in whom this process is deficient, and for minimising damage in patients where the process is overactive. 
  • Thescientists at theMedical Research Council's National Institute for Medical Research worked with colleagues from the University of Aberdeen. The work was supported by the Medical Research Council and the Wellcome Trust.