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 responded to the presence of IL-5 driven eosinophils at the outset of infection.(A) Topical injection of recombinant IL-5 (rIL5) resulted in a local subcutaneous increase (p = 0.05, Wilcoxon rank-sum test, n = 5) but no systemic increase in eosinophil recruitment relative to other lymphocyte populations. (B) The addition of rIL5 upon inoculation of infective larvae to BALB/c mice accelerated their growth before their 3rd larval moult, at D7 p.i. (* p = 0.019, unpaired two-tailed t-test; n = 30, no significant effect of mouse). This occurred independently of mouse genetic background as similar data were obtained in BALB/c and in C57BL/6 mice. (C) The depletion of eosinophils by α-CCR3 antibody treatment 24 h before infection resulted in a prolonged reduction of eosinophilia and (D) in a slower larval development that were not rescued by the addition of rIL-5 (p = 0.003, ANOVA and Dunn's multiple comparison post test: ** p<0.01; * p<0.05; n = 19 to 23). None of the treatments affected larval survival (see Figure S2C). Error bars depict s.e.m.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2957396&req=5

pbio-1000525-g002: Filarial nematodes responded to the presence of IL-5 driven eosinophils at the outset of infection.(A) Topical injection of recombinant IL-5 (rIL5) resulted in a local subcutaneous increase (p = 0.05, Wilcoxon rank-sum test, n = 5) but no systemic increase in eosinophil recruitment relative to other lymphocyte populations. (B) The addition of rIL5 upon inoculation of infective larvae to BALB/c mice accelerated their growth before their 3rd larval moult, at D7 p.i. (* p = 0.019, unpaired two-tailed t-test; n = 30, no significant effect of mouse). This occurred independently of mouse genetic background as similar data were obtained in BALB/c and in C57BL/6 mice. (C) The depletion of eosinophils by α-CCR3 antibody treatment 24 h before infection resulted in a prolonged reduction of eosinophilia and (D) in a slower larval development that were not rescued by the addition of rIL-5 (p = 0.003, ANOVA and Dunn's multiple comparison post test: ** p<0.01; * p<0.05; n = 19 to 23). None of the treatments affected larval survival (see Figure S2C). Error bars depict s.e.m.

Mentions: We then wanted to establish how soon L. sigmodontis life-history traits were determined by their new environment because larvae migrate away from the inflamed subcutaneous tissue within hours of their inoculation [48], reaching the pleural cavity within 4 d while still at the L3 stage [31]. Our results above implicate IL-5 driven eosinophils in accelerating the parasites' development, either directly or through their downstream products. We thus included recombinant IL-5 (rIL-5) in the inoculum containing infective larvae. This would ensure that the parasites be exposed to rIL-5 only until they migrated away or until rIL-5 was degraded—thus for no more than 4 d. We confirmed that the administration of rIL-5 increased local subcutaneous eosinophilia in comparison to a standard protein control of bovine albumin (BSA), while no systemic increase in eosinophilia was observed (Figure 2A). Systemic concentrations of IL-4, IL-5, IL-10, IFN-γ, IgG1, and IgG2a were unaffected by the administration of rIL-5 (unpublished data). This transient presence of rIL-5 and eosinophils resulted in accelerated growth of the larvae as early as D7 p.i. when compared to BSA controls in BALB/c mice (Figure 2B) and in C57BL/6 mice (unpublished data). Consequently, filarial nematodes are able to adjust their development to the immune environment as soon as they enter the host, and this effect is independent of mouse genetic background.


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 responded to the presence of IL-5 driven eosinophils at the outset of infection.(A) Topical injection of recombinant IL-5 (rIL5) resulted in a local subcutaneous increase (p = 0.05, Wilcoxon rank-sum test, n = 5) but no systemic increase in eosinophil recruitment relative to other lymphocyte populations. (B) The addition of rIL5 upon inoculation of infective larvae to BALB/c mice accelerated their growth before their 3rd larval moult, at D7 p.i. (* p = 0.019, unpaired two-tailed t-test; n = 30, no significant effect of mouse). This occurred independently of mouse genetic background as similar data were obtained in BALB/c and in C57BL/6 mice. (C) The depletion of eosinophils by α-CCR3 antibody treatment 24 h before infection resulted in a prolonged reduction of eosinophilia and (D) in a slower larval development that were not rescued by the addition of rIL-5 (p = 0.003, ANOVA and Dunn's multiple comparison post test: ** p<0.01; * p<0.05; n = 19 to 23). None of the treatments affected larval survival (see Figure S2C). Error bars depict s.e.m.
© Copyright Policy
Related In: Results  -  Collection

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

pbio-1000525-g002: Filarial nematodes responded to the presence of IL-5 driven eosinophils at the outset of infection.(A) Topical injection of recombinant IL-5 (rIL5) resulted in a local subcutaneous increase (p = 0.05, Wilcoxon rank-sum test, n = 5) but no systemic increase in eosinophil recruitment relative to other lymphocyte populations. (B) The addition of rIL5 upon inoculation of infective larvae to BALB/c mice accelerated their growth before their 3rd larval moult, at D7 p.i. (* p = 0.019, unpaired two-tailed t-test; n = 30, no significant effect of mouse). This occurred independently of mouse genetic background as similar data were obtained in BALB/c and in C57BL/6 mice. (C) The depletion of eosinophils by α-CCR3 antibody treatment 24 h before infection resulted in a prolonged reduction of eosinophilia and (D) in a slower larval development that were not rescued by the addition of rIL-5 (p = 0.003, ANOVA and Dunn's multiple comparison post test: ** p<0.01; * p<0.05; n = 19 to 23). None of the treatments affected larval survival (see Figure S2C). Error bars depict s.e.m.
Mentions: We then wanted to establish how soon L. sigmodontis life-history traits were determined by their new environment because larvae migrate away from the inflamed subcutaneous tissue within hours of their inoculation [48], reaching the pleural cavity within 4 d while still at the L3 stage [31]. Our results above implicate IL-5 driven eosinophils in accelerating the parasites' development, either directly or through their downstream products. We thus included recombinant IL-5 (rIL-5) in the inoculum containing infective larvae. This would ensure that the parasites be exposed to rIL-5 only until they migrated away or until rIL-5 was degraded—thus for no more than 4 d. We confirmed that the administration of rIL-5 increased local subcutaneous eosinophilia in comparison to a standard protein control of bovine albumin (BSA), while no systemic increase in eosinophilia was observed (Figure 2A). Systemic concentrations of IL-4, IL-5, IL-10, IFN-γ, IgG1, and IgG2a were unaffected by the administration of rIL-5 (unpublished data). This transient presence of rIL-5 and eosinophils resulted in accelerated growth of the larvae as early as D7 p.i. when compared to BSA controls in BALB/c mice (Figure 2B) and in C57BL/6 mice (unpublished data). Consequently, filarial nematodes are able to adjust their development to the immune environment as soon as they enter the host, and this effect is independent of mouse genetic background.

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