Limits...
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.

Show MeSH

Related in: MedlinePlus

Filarial nematodes developed faster when IL-5 driven eosinophils were present.Litomosoides sigmodontis filarial nematodes developed slower during their larval stages in IL-5 deficient (IL-5−/−) mice than in C57BL/6 wild type controls as measured (A) by their shorter lengths (** p = 0.015, ANOVA; n = 50 larvae nested in 5 mice per group) and (B) by their delayed moulting to the 4th larval stage at D10 p.i. (** p = 0.0007, Chi2 test; n = 5 mice). (C) At D30 p.i., however, no differences in the moulting rate to the adult stage were observed between IL-5−/− mice and wild type controls (n = 5 mice). The constitutive absence of eosinophils in PHIL mice resulted in slower larval development as judged by (D) their lengths in both male and female mice (*, p = 0.04 for the effect of mouse strain when variation due to mouse sex is accounted for, GLM; n = 57 to 59 in 7 mice) and by (E) their moulting rates (p = 0.02, Fisher Exact Test; n = 7 mice) at D12 p.i. as compared to C57BL/6 wild type controls. None of the treatments affected larval survival (see Figure S2A and S2B). Error bars depict s.e.m.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2957396&req=5

pbio-1000525-g001: Filarial nematodes developed faster when IL-5 driven eosinophils were present.Litomosoides sigmodontis filarial nematodes developed slower during their larval stages in IL-5 deficient (IL-5−/−) mice than in C57BL/6 wild type controls as measured (A) by their shorter lengths (** p = 0.015, ANOVA; n = 50 larvae nested in 5 mice per group) and (B) by their delayed moulting to the 4th larval stage at D10 p.i. (** p = 0.0007, Chi2 test; n = 5 mice). (C) At D30 p.i., however, no differences in the moulting rate to the adult stage were observed between IL-5−/− mice and wild type controls (n = 5 mice). The constitutive absence of eosinophils in PHIL mice resulted in slower larval development as judged by (D) their lengths in both male and female mice (*, p = 0.04 for the effect of mouse strain when variation due to mouse sex is accounted for, GLM; n = 57 to 59 in 7 mice) and by (E) their moulting rates (p = 0.02, Fisher Exact Test; n = 7 mice) at D12 p.i. as compared to C57BL/6 wild type controls. None of the treatments affected larval survival (see Figure S2A and S2B). Error bars depict s.e.m.

Mentions: Interleukin-5 (IL-5), a major element of the T helper 2 (Th2) type effector response, is responsible for vaccine-induced protection and resolution of filarial infection [22],[33],[39] and thus a likely candidate for the developmental cue used by L. sigmodontis [33],[44]. In homozygous IL-5 deficient mice (IL-5−/−), the absence of IL-5 had no effect on the establishment of the filariae when compared to C57BL/6 wild type controls, confirming previous data in primary infections (Figure S2A) [45]. However, 10 d post infection (D10 p.i.), filarial development was delayed in the IL-5 deficient mice, as larvae were significantly smaller (Figure 1A), and fewer had reached the fourth larval stage (L4) (Figure 1B) than in wild type controls. However, at D30 p.i., the proportions of the different stages were identical (20% L4, 15% undergoing their moult, and 65% adults; Figure 1C), suggesting that early growth retardation is not necessarily permanent. Because IL-5 acts through eosinophils to kill filarial parasites, these cells may mediate the early variations in larval development. Furthermore, there have been reports that eosinophilia correlates with the size of another nematode, Teladorsagia circumcincta [28]. To confirm that IL-5 was acting via eosinophils, we inoculated L. sigmodontis into PHIL mice that lack the eosinophil lineage entirely [46]. In these mice the filariae developed slower than in wild type C57BL/6 controls as measured by both their lengths and moulting rate (Figure 1D and 1E). Given our previous findings that no difference in larval development is observed between large and small doses of infective larvae [47], resource availability is unlikely to explain the observed differences. Taken together, these results show that the growth and moulting acceleration mediated by IL-5 and eosinophils are morphologically detectable in the early phases of larval development only, and that variations in larval development are not due to differential survival nor to competition for resources between the infective larvae.


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)

Filarial nematodes developed faster when IL-5 driven eosinophils were present.Litomosoides sigmodontis filarial nematodes developed slower during their larval stages in IL-5 deficient (IL-5−/−) mice than in C57BL/6 wild type controls as measured (A) by their shorter lengths (** p = 0.015, ANOVA; n = 50 larvae nested in 5 mice per group) and (B) by their delayed moulting to the 4th larval stage at D10 p.i. (** p = 0.0007, Chi2 test; n = 5 mice). (C) At D30 p.i., however, no differences in the moulting rate to the adult stage were observed between IL-5−/− mice and wild type controls (n = 5 mice). The constitutive absence of eosinophils in PHIL mice resulted in slower larval development as judged by (D) their lengths in both male and female mice (*, p = 0.04 for the effect of mouse strain when variation due to mouse sex is accounted for, GLM; n = 57 to 59 in 7 mice) and by (E) their moulting rates (p = 0.02, Fisher Exact Test; n = 7 mice) at D12 p.i. as compared to C57BL/6 wild type controls. None of the treatments affected larval survival (see Figure S2A and S2B). Error bars depict s.e.m.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2957396&req=5

pbio-1000525-g001: Filarial nematodes developed faster when IL-5 driven eosinophils were present.Litomosoides sigmodontis filarial nematodes developed slower during their larval stages in IL-5 deficient (IL-5−/−) mice than in C57BL/6 wild type controls as measured (A) by their shorter lengths (** p = 0.015, ANOVA; n = 50 larvae nested in 5 mice per group) and (B) by their delayed moulting to the 4th larval stage at D10 p.i. (** p = 0.0007, Chi2 test; n = 5 mice). (C) At D30 p.i., however, no differences in the moulting rate to the adult stage were observed between IL-5−/− mice and wild type controls (n = 5 mice). The constitutive absence of eosinophils in PHIL mice resulted in slower larval development as judged by (D) their lengths in both male and female mice (*, p = 0.04 for the effect of mouse strain when variation due to mouse sex is accounted for, GLM; n = 57 to 59 in 7 mice) and by (E) their moulting rates (p = 0.02, Fisher Exact Test; n = 7 mice) at D12 p.i. as compared to C57BL/6 wild type controls. None of the treatments affected larval survival (see Figure S2A and S2B). Error bars depict s.e.m.
Mentions: Interleukin-5 (IL-5), a major element of the T helper 2 (Th2) type effector response, is responsible for vaccine-induced protection and resolution of filarial infection [22],[33],[39] and thus a likely candidate for the developmental cue used by L. sigmodontis [33],[44]. In homozygous IL-5 deficient mice (IL-5−/−), the absence of IL-5 had no effect on the establishment of the filariae when compared to C57BL/6 wild type controls, confirming previous data in primary infections (Figure S2A) [45]. However, 10 d post infection (D10 p.i.), filarial development was delayed in the IL-5 deficient mice, as larvae were significantly smaller (Figure 1A), and fewer had reached the fourth larval stage (L4) (Figure 1B) than in wild type controls. However, at D30 p.i., the proportions of the different stages were identical (20% L4, 15% undergoing their moult, and 65% adults; Figure 1C), suggesting that early growth retardation is not necessarily permanent. Because IL-5 acts through eosinophils to kill filarial parasites, these cells may mediate the early variations in larval development. Furthermore, there have been reports that eosinophilia correlates with the size of another nematode, Teladorsagia circumcincta [28]. To confirm that IL-5 was acting via eosinophils, we inoculated L. sigmodontis into PHIL mice that lack the eosinophil lineage entirely [46]. In these mice the filariae developed slower than in wild type C57BL/6 controls as measured by both their lengths and moulting rate (Figure 1D and 1E). Given our previous findings that no difference in larval development is observed between large and small doses of infective larvae [47], resource availability is unlikely to explain the observed differences. Taken together, these results show that the growth and moulting acceleration mediated by IL-5 and eosinophils are morphologically detectable in the early phases of larval development only, and that variations in larval development are not due to differential survival nor to competition for resources between the infective larvae.

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