The Role of Immune-Mediated Apparent Competition in Genetically Diverse Malaria Infections

Abstract

Competitive interactions between coinfecting genotypes of the same pathogen can impose selection on virulence, but the direction of this selection depends on the mechanisms behind the interactions. Here, we investigate how host immune responses contribute to competition between clones in mixed infections of the rodent malaria parasite Plasmodium chabaudi. We studied single and mixed infections of a virulent and an avirulent clone and compared the extent of competition in immunodeficient and immunocompetent mice (nude mice and T cell-reconstituted nude mice, respectively). In immunocompetent mice, the avirulent clone suffered more from competition than did the virulent clone. The competitive suppression of the avirulent clone was alleviated in immunodeficient mice. Moreover, the relative density of the avirulent clone in mixed infections was higher in immunodeficient than in immunocompetent mice. We conclude that immune-mediated interactions contributed to competitive suppression of the avirulent clone, although other mechanisms, presumably competition for resources such as red blood cells, must also be important. Because only the avirulent clone suffered from immune-mediated competition, this mechanism should contribute to selection for increased virulence in mixed infections in this host-parasite system. As far as we are aware, this is the first direct experimental evidence of immune-mediated apparent competition in any host-parasite system.

Within-host competition betweenBorrelia afzelii ospCstrains in wild hosts as revealed by massively parallel amplicon sequencing

“…Second, co-infecting strains may compete over some limiting resource. Third, there can be immune-mediated competition, if the immune response is strain-transcending and multiple infections induce a stronger immune response than single infections (for example, because multiple infections have higher infection intensities during the early phase of the infection, before infection intensities are regulated by the immune response) [34,35]. Which of these mechanisms is most important in the case of B. afzelii?…”

“…It is difficult to elucidate the relative importance of different types of competition from the current dataset. Instead, infection experiments where different aspects of the host phenotype are modified are required [34,35].…”

“…The quality of the sequences was inspected with FastQC [21] and the first 245 bp of ospC that were critical for annotation (see below) had a satisfactory average quality score per base of 30 (range 20 -38). For rrs-rrlA IGS, the average quality score per base for the full length sequences was above 30 (range [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. Demultiplexing of individual samples for the ospC dataset was done with the software GENEIOUS (v. 5.0, Biomatters, Auckland, New Zealand) that handles Roche's MID set.…”

The evolution of drug resistance and the curious orthodoxy of aggressive chemotherapy

“…However, in a rodent malaria model, P. chabaudi in laboratory mice, we and others have experimentally demonstrated that densities of individual clones within an infection are severely suppressed when coinfecting clones are present (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44). This competitive suppression substantially reduces the density of transmission stages (42,43), and hence transmission of individual clones to mosquitoes (33,35,36).…”

A symbiont's dispersal strategy: condition-dependent dispersal underlies predictable variation in direct transmission among hosts

“…Even at the within-host level, within-host microhabitats or tissues may vary with respect to the resources they offer or the risk of mortality to symbionts [11][12][13]. Moreover, each host and each microhabitat offers limited resources which are partitioned among symbionts creating the possibility of strong inter-and intraspecific competition among symbionts sharing a host [14][15][16]. Because hosts are variable in qualities that can directly influence symbiont fitness, it is probable that natural selection favours symbionts that move among hosts discriminately, just as free-living organisms display evolved condition-dependent dispersal strategies [17][18][19].…”