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Filarial parasites develop faster and reproduce earlier in response to host immune effectors that determine filarial life expectancy.

Babayan SA, Read AF, Lawrence RA, Bain O, Allen JE - PLoS Biol. (2010)

Bottom Line: Consequently they produce microfilariae, their transmission stages, earlier and in greater numbers.Filarial nematodes are therefore able to adjust their reproductive schedules in response to an environmental predictor of their probability of survival, as proposed by evolutionary theory, thereby mitigating the effects of the immune attack to which helminths are most susceptible.Enhancing protective immunity against filarial nematodes, for example through vaccination, may be less effective at reducing transmission than would be expected and may, at worst, lead to increased transmission and, hence, pathology.

View Article: PubMed Central - PubMed

Affiliation: Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom. s.babayan@ed.ac.uk

ABSTRACT
Humans and other mammals mount vigorous immune assaults against helminth parasites, yet there are intriguing reports that the immune response can enhance rather than impair parasite development. It has been hypothesized that helminths, like many free-living organisms, should optimize their development and reproduction in response to cues predicting future life expectancy. However, immune-dependent development by helminth parasites has so far eluded such evolutionary explanation. By manipulating various arms of the immune response of experimental hosts, we show that filarial nematodes, the parasites responsible for debilitating diseases in humans like river blindness and elephantiasis, accelerate their development in response to the IL-5 driven eosinophilia they encounter when infecting a host. Consequently they produce microfilariae, their transmission stages, earlier and in greater numbers. Eosinophilia is a primary host determinant of filarial life expectancy, operating both at larval and at late adult stages in anatomically and temporally separate locations, and is implicated in vaccine-mediated protection. Filarial nematodes are therefore able to adjust their reproductive schedules in response to an environmental predictor of their probability of survival, as proposed by evolutionary theory, thereby mitigating the effects of the immune attack to which helminths are most susceptible. Enhancing protective immunity against filarial nematodes, for example through vaccination, may be less effective at reducing transmission than would be expected and may, at worst, lead to increased transmission and, hence, pathology.

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Early eosinophilia enhances L. sigmodontis reproductive output.(A) When co-inoculated with eosinophilia-inducing rIL-5 and L3 parasites, BALB/c mice became microfilaraemic sooner than in control infections as suggested by the proportion of mice presenting blood circulating microfilariae by D55 p.i. (p = 0.08, Fisher's exact test, n = 17, analysis restricted to mice that became microfilaraemic). (B) Early rIL-5-induced eosinophilia resulted in increased microfilaraemia throughout patency (effect of treatment on microfilaraemia p = 0.0001, negative binomial glm; n = 12, data points represent means ± s.e.m.) and a marginally earlier peak in microfilaraemia (occurring on day 68.5±1 and 72.8±2 in treated mice and controls, respectively, p = 0.09).
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pbio-1000525-g004: Early eosinophilia enhances L. sigmodontis reproductive output.(A) When co-inoculated with eosinophilia-inducing rIL-5 and L3 parasites, BALB/c mice became microfilaraemic sooner than in control infections as suggested by the proportion of mice presenting blood circulating microfilariae by D55 p.i. (p = 0.08, Fisher's exact test, n = 17, analysis restricted to mice that became microfilaraemic). (B) Early rIL-5-induced eosinophilia resulted in increased microfilaraemia throughout patency (effect of treatment on microfilaraemia p = 0.0001, negative binomial glm; n = 12, data points represent means ± s.e.m.) and a marginally earlier peak in microfilaraemia (occurring on day 68.5±1 and 72.8±2 in treated mice and controls, respectively, p = 0.09).

Mentions: If larval developmental plasticity in the face of protective immune responses is indeed an adaptive (fitness-enhancing) trait of L. sigmodontis, the IL-5 mediated acceleration of parasite development should lead to greater reproduction earlier in infection [12]. We thus assessed the relationship between the presence of IL-5 and eosinophils at the site of inoculation and worm fertility 2 mo later. We injected larvae together with rIL-5 to mice as described above to ensure that eosinophilia would peak locally and early in the infection and then return to levels of control mice thereafter. When larvae were injected with rIL-5, the onset of patency (detection of microfilariae) occurred earlier than in control infections (Figure 4A). After D70 p.i., no difference in microfilaria prevalence was observed between treatment groups. Thus, a local and transiently increased eosinophilia reduces the age at which females are able to release microfilariae into the peripheral circulation. The faster larval development triggered by the addition of rIL-5 upon infection (see Figure 2B, 2D) also resulted in an increased microfilaraemia in the peripheral blood compared to control mice throughout patency (Figure 4B). Additionally, because IL-4 has been shown to specifically control microfilaraemia [39], we wanted to assess whether our observations were due to a rIL-5-driven alteration of IL-4 in susceptible genotypes. In both wild type and IL-4−/− BALB/c mice, rIL-5 treatment increased overall microfilaraemia 5–8-fold over BSA-injected controls (Table 1). While there were vastly superior numbers of circulating microfilariae in IL-4−/− mice as compared to BALB/c mice, in both strains rIL-5 treatment resulted in a similar increase of the overall number of microfilariae in the peripheral circulation throughout patency (Table 1). Thus the impact of early eosinophilia on fecundity was independent of the effector pathways associated with immunity against microfilariae.


Filarial parasites develop faster and reproduce earlier in response to host immune effectors that determine filarial life expectancy.

Babayan SA, Read AF, Lawrence RA, Bain O, Allen JE - PLoS Biol. (2010)

Early eosinophilia enhances L. sigmodontis reproductive output.(A) When co-inoculated with eosinophilia-inducing rIL-5 and L3 parasites, BALB/c mice became microfilaraemic sooner than in control infections as suggested by the proportion of mice presenting blood circulating microfilariae by D55 p.i. (p = 0.08, Fisher's exact test, n = 17, analysis restricted to mice that became microfilaraemic). (B) Early rIL-5-induced eosinophilia resulted in increased microfilaraemia throughout patency (effect of treatment on microfilaraemia p = 0.0001, negative binomial glm; n = 12, data points represent means ± s.e.m.) and a marginally earlier peak in microfilaraemia (occurring on day 68.5±1 and 72.8±2 in treated mice and controls, respectively, p = 0.09).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2957396&req=5

pbio-1000525-g004: Early eosinophilia enhances L. sigmodontis reproductive output.(A) When co-inoculated with eosinophilia-inducing rIL-5 and L3 parasites, BALB/c mice became microfilaraemic sooner than in control infections as suggested by the proportion of mice presenting blood circulating microfilariae by D55 p.i. (p = 0.08, Fisher's exact test, n = 17, analysis restricted to mice that became microfilaraemic). (B) Early rIL-5-induced eosinophilia resulted in increased microfilaraemia throughout patency (effect of treatment on microfilaraemia p = 0.0001, negative binomial glm; n = 12, data points represent means ± s.e.m.) and a marginally earlier peak in microfilaraemia (occurring on day 68.5±1 and 72.8±2 in treated mice and controls, respectively, p = 0.09).
Mentions: If larval developmental plasticity in the face of protective immune responses is indeed an adaptive (fitness-enhancing) trait of L. sigmodontis, the IL-5 mediated acceleration of parasite development should lead to greater reproduction earlier in infection [12]. We thus assessed the relationship between the presence of IL-5 and eosinophils at the site of inoculation and worm fertility 2 mo later. We injected larvae together with rIL-5 to mice as described above to ensure that eosinophilia would peak locally and early in the infection and then return to levels of control mice thereafter. When larvae were injected with rIL-5, the onset of patency (detection of microfilariae) occurred earlier than in control infections (Figure 4A). After D70 p.i., no difference in microfilaria prevalence was observed between treatment groups. Thus, a local and transiently increased eosinophilia reduces the age at which females are able to release microfilariae into the peripheral circulation. The faster larval development triggered by the addition of rIL-5 upon infection (see Figure 2B, 2D) also resulted in an increased microfilaraemia in the peripheral blood compared to control mice throughout patency (Figure 4B). Additionally, because IL-4 has been shown to specifically control microfilaraemia [39], we wanted to assess whether our observations were due to a rIL-5-driven alteration of IL-4 in susceptible genotypes. In both wild type and IL-4−/− BALB/c mice, rIL-5 treatment increased overall microfilaraemia 5–8-fold over BSA-injected controls (Table 1). While there were vastly superior numbers of circulating microfilariae in IL-4−/− mice as compared to BALB/c mice, in both strains rIL-5 treatment resulted in a similar increase of the overall number of microfilariae in the peripheral circulation throughout patency (Table 1). Thus the impact of early eosinophilia on fecundity was independent of the effector pathways associated with immunity against microfilariae.

Bottom Line: Consequently they produce microfilariae, their transmission stages, earlier and in greater numbers.Filarial nematodes are therefore able to adjust their reproductive schedules in response to an environmental predictor of their probability of survival, as proposed by evolutionary theory, thereby mitigating the effects of the immune attack to which helminths are most susceptible.Enhancing protective immunity against filarial nematodes, for example through vaccination, may be less effective at reducing transmission than would be expected and may, at worst, lead to increased transmission and, hence, pathology.

View Article: PubMed Central - PubMed

Affiliation: Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom. s.babayan@ed.ac.uk

ABSTRACT
Humans and other mammals mount vigorous immune assaults against helminth parasites, yet there are intriguing reports that the immune response can enhance rather than impair parasite development. It has been hypothesized that helminths, like many free-living organisms, should optimize their development and reproduction in response to cues predicting future life expectancy. However, immune-dependent development by helminth parasites has so far eluded such evolutionary explanation. By manipulating various arms of the immune response of experimental hosts, we show that filarial nematodes, the parasites responsible for debilitating diseases in humans like river blindness and elephantiasis, accelerate their development in response to the IL-5 driven eosinophilia they encounter when infecting a host. Consequently they produce microfilariae, their transmission stages, earlier and in greater numbers. Eosinophilia is a primary host determinant of filarial life expectancy, operating both at larval and at late adult stages in anatomically and temporally separate locations, and is implicated in vaccine-mediated protection. Filarial nematodes are therefore able to adjust their reproductive schedules in response to an environmental predictor of their probability of survival, as proposed by evolutionary theory, thereby mitigating the effects of the immune attack to which helminths are most susceptible. Enhancing protective immunity against filarial nematodes, for example through vaccination, may be less effective at reducing transmission than would be expected and may, at worst, lead to increased transmission and, hence, pathology.

Show MeSH
Related in: MedlinePlus