Immunology meets epidemiology: A closer look at super spreaders

Posted by Kasra

Recent work by Gopinath et al. published in PLoS Pathogens touches a crucial issue in epidemiology of infectious diseases. We tend to look at infectious diseases as infecting everyone more or less uniformly. But many studies have shown that a great extent of heterogeneity exists in the amount of pathogen that is spread from infected individuals. The common rule is a 80-20 rule: it says that 20% of infected individuals account for 80% of disease spread. To learn more about this phenomenon and the research behind it, you can have a look at this comment published in Nature news and views. This rule appears to stand for many infectious diseases capable of causing epidemics. Therefore, studying and identifying the super spreaders –  or as this study puts them super shedders –  is of critical importance.  This study has tried to shed some light on the differences of the immune system of these individuals compared to normal shedders.

The authors use a special model of Salmonella enterica infection of mice where longterm infection was sustainable without the mice succumbing to disease. They then compared mice that very high numbers of bacteria present in their stool (two logs higher than what is normally expected of moderate shedders) with normally infected mice.

Comparing the immune response between moderate and supper shedders, the authors find that although the bacterial load in the gastrointestinal tract is highly different between the two groups of mice, the amount of bacteria in systemic organs such as the spleen is the same, so is the overall appearance of the mice. However, they find an enhanced innate immune response in the supper shedders marked with higher IL-6, a pro-inflammatory cytokine, in the serum and more neutrophils in the blood and other organs. On the other hand, they observe a reduction in the ratio of Th1 lymphocytes to regulatory T cells. The authors also found Th1 cells to be less responsive to proliferation-inducing cytokine IL-2.

Interestingly, the authors were able to induce some of the super shedder ‘characteristics’ by giving streptomycin to moderate shedder mice, probably giving room for Salmonella to expand in the altered microbiota. This further suggests that the observed immune characteristics are due to the bacterial load present in the gut. Finally, they look at the possible connection between neutrophil expansion and reduction in Th1 responsiveness.

Immunological differences between super shedder and moderate shedder Salmonella infected mice

The authors argue that to the be able to contain such a high bacterial load in the body, the organism would either have a weaker inflammatory response, or a way to dampen adaptive response to reduce the cost of high inflammation to the body. This is among the first steps in understanding the nature of the immune response in super spreaders. It would be interesting to see if this is a general theme in all host-pathogen interactions when super spreading occurs, or if it is different with every pathogen. This kind of research can importantly lead to better understanding of the immune response and hopefully also molecular markers that would help rapid identification the super spreaders and better control of disease outbreaks.

Gopinath S, Hotson A, Johns J, Nolan G, & Monack D (2013). The Systemic Immune State of Super-shedder Mice Is Characterized by a Unique Neutrophil-dependent Blunting of TH1 Responses. PLoS pathogens, 9 (6) PMID: 23754944

Galvani AP, & May RM (2005). Epidemiology: dimensions of superspreading. Nature, 438 (7066), 293-5 PMID: 16292292