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

ResearchBlogging.org

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An intracellular receptor for antibodies

Posted by: Kasra

We usually consider exiting the phagolysosome and entering the cell cytoplasm to be a immune evasion mechanism for pathogens. The pathogens inside the phagolysosome can be processed and presented via MHCII to the adaptive immune system, but once free of that compartment, the pathogen could potentially ‘hide’ from the immune system, well apparently not that much! Apart from the intracellular pattern recognition receptors (NLRs), researchers have found another receptor that responds to intracellular presence of antibodies. McEwan et al. showed that if antibody coated viruses or bacteria have entered the cytosol, presence of the Fc part of the antibody can be sensed by a protein called TRIM21. This could in turn result in an inflammatory and anti-viral response by activating NF-κB and AP-1 and production of cytokines. To me, this is an excellent example that shows how the host and the pathogens have evolved together for many years becoming more and more complex through an arms race.  A newly developed strategy by one party is followed by a counter strategy by the other party.

NatImm

From Geijtenbeek TB, & Gringhuis SI (2013). An inside job for antibodies: tagging pathogens for intracellular sensing. Nature immunology, 14 (4), 309-11 PMID: 23507635

McEwan WA, Tam JC, Watkinson RE, Bidgood SR, Mallery DL, & James LC (2013). Intracellular antibody-bound pathogens stimulate immune signaling via the Fc receptor TRIM21. Nature immunology, 14 (4), 327-36 PMID: 23455675

Geijtenbeek TB, & Gringhuis SI (2013). An inside job for antibodies: tagging pathogens for intracellular sensing. Nature immunology, 14 (4), 309-11 PMID: 23507635

ResearchBlogging.org