Developing worms need the host immune system.

Abstract

Schistosomes are important parasites of humans and other animals. Considerable effort has gone into trying to understand how they persist in their vertebrate hosts in the face of the immune system. Recent work has found that developing schistosomes need components of the host immune system to complete their development [1xModulation of blood fluke development in the liver by hepatic CD4+ lymphocytes. Davies, S.J. et al. Science. 2001; 294: 1358–1361Crossref | PubMed | Scopus (100)See all References[1]. This is remarkable because it is generally held that the host immune response acts against parasites, with the corollary that worm infections can be fitter and more fecund in immunologically deficient animals.When immunologically normal mice are infected with cercariae, the parasite migrates through the host body and arrives in the portal veins where the worms grow and commence egg production. In hosts deficient in B and T cells, worms are significantly smaller and less developed compared with worms from control animals. This delayed development is not a result of the late arrival of migrating worms in the portal veins because arrival times did not vary between normal and immunodeficient mice. Significantly, worms from the immunodeficient mice delayed the start of their egg production and had reduced rates of egg production, although these eggs were fully viable, as measured by their ability to hatch miracidia that were infective to the gastropod intermediate host. Further analysis identified a liver-specific sub-population of lymphocytes (CD4+ TCR β+ cells) that were required for normal schistosome development.This work clearly shows that developing schistosomes use cues from the host immune system to develop ‘normally’. Davies et al. conclude that schistosomes have an alternative developmental pathway (slowed development, reduced egg production) that occurs in the absence of these cues. However, there are other interpretations. It seems unlikely that stunted development and reduced egg production are adaptive phenotypes; rather, are they just very ‘ill’ worms? Might these observations explain some aspects of host specificity of parasites? Host specificity is often seen as the failure of an infection to ‘take’ in the ‘wrong’ host. Here, the absence of host cues (presumably from CD4+ TCR β+ cells) prevents worms from thriving, just as worms might fail to thrive in ‘wrong’ hosts similarly as a result of the absence of necessary cues. But why do developing worms need these cues at all? It would seem so much easier to be a parasite that grows and develops in any host and takes a chance with the host physiology and immune system as necessary.More broadly, these results are resonant with other observations. Infections of the nematode Strongyloides ratti in immunologically compromised rats have a lower initial reproductive output compared with infections in normal or previously immunised animals. These data were interpreted in relation to the facultative adjustment of nematode maturation time in response to varying host immune pressure, with delayed development (but greater life-time fitness) favoured under immune stress. Also, the filarial nematode Brugia malayi is only able to develop in immunodeficient mice which have natural killer (NK) cells, suggesting that B. malayi infection requires NK cells, or a product of them, for growth and development.The host immune response exists to resist infections, including those of nematodes and trematodes. However, it seems that these parasites have evolved to require the presence of some aspect of the host immune system for their normal development. Understanding this paradox must be a research challenge for the future.