Persistence of parasites in the host: co-evolution of parasitism and immunity

Posted by: Kasra Hassani

Many pathogens are unable to live outside the host. Therefore, before killing or completely using up their host, they should ensure that they will be successfully transfered to another one, or one may say, those who did not never made it through evolution. Depending on their life-cycle and type, strategies to ensure transmission diffes among pathogens. In a comment for Nature Reviews in Immunology Sacks and Yazdanbakhsh comparatively discuss these strategies among air-borne pathogens, protozoan vector borne pathogens and also multicellular pathogens. Air-borne bacteria and viruses can easily spread after an acute infection and do not necessarily need to modulate immune response to avoid the up-coming sterilizing immunity. On the other hand, vector-borne parasites such as Plasmodium or the Trypanosomes require more time for efficient transmission. Therefore, parasites have developed strategies to delay life-long immunity. For instance, in African Trypanosomes (T. brucei) continuous variation of the surface glycoprotein (correctly named the variable surface glycoprotein or VSG) hiders development of a protective immune response and allows the parasite to reside in the blood for a long time. Alternatively, Leishmania infections co-inside with presence of regulatory T cells and considerable amounts of IL-10 which down-regulates the protective Th1 response. In larger parasites such as helminths rapid movement from immune-sensitive areas such as the skin or acquiring and presentation of host antigens are among the strategies that are used for delaying the immune response and buying time for transmission.

What I find more interesting among all of this is the evolution of the host in the same direction. In many parasitic infections, the immune response does not lead to complete parasite clearance, rather to a residual infection with minimum or no pathology yet still transmissibility.  Read et al. have argued in a Primer in PLoS Biology that this ‘tolerance’ is a type of immunity that can arise in the host-parasite co-evolution as an alternative to ‘resistance’ where complete of the pathogen clearance occurs. Firstly, complete clearance of the pathogen can be too costly compared to its control. Secondly, In the dynamic co-evolution of the host and the parasite, genes who confer tolerance against a pathogen could be favored to those who confer resistance. Evolution of tolerance does not harm or might even favor parasite existence since tolerant host are reservoirs of the parasites within the population. Therefore, they do not prompt counter-adaptation by the parasites.

Sacks and Yazdanbakhsh conclude their comment by mentioning that these immune strategies should be taken into consideration when designing vaccines for parasitic diseases. They suggest that instead of trying to override this desire of the immune system for tolerance rather than resistance, vaccines could induce tolerance where minimal pathology is caused by a controlled persistence of the parasites. A classic example of a vaccination strategy in this line is Leishmanization wherein live Leishmania parasites used to be inoculated in soldiers or children in risk of infection and would confer immunity to further infections. With regard to development of immunological tolerance to leishmaniasis, not resistance, these types of vaccines need reconsideration.