Low-dose immune challenges result in detectable levels of oxidative damage

Armour, Ellen M.; Bruner, Taylor L.; Hines, Justin K.; Butler, Michael W.

doi:10.1242/jeb.220095

Cited by 27 publications

(23 citation statements)

References 83 publications

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“…Each of these steps is often costly and can cause self-damage, such as the energetic cost of initiating and maintaining an activated state (Ganeshan & Chawla 2014), the risk of autoimmune responses (recognition), or oxidative stress from effector response itself (Viney et al 2005). Therefore, hosts should avoid initiating immune responses unnecessarily, and when activated, must able to turn off or modulate this response at the appropriate time, not prematurely, but also not too late as to impose excess cost once the danger has passed (Khan et al 2017;Armour et al 2020). Variation at any stage of the response can lead to differences in infection outcomes and immunopathology side-effects, yet when we only examine the end result, we do not know at which step variation occurred.…”

Section: Introductionmentioning

confidence: 99%

Rapid Evolution of Parasite Resistance via Improved Recognition and Accelerated Immune Activation and Deactivation

Hund

et al. 2020

Preprint

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ABSTRACTClosely related populations often differ in resistance to a given parasite, as measured by infection success or failure. Yet, the immunological mechanisms of these evolved differences are rarely specified. Does resistance evolve via changes to the host’s ability to recognize that an infection exists, actuate an effective immune response, or attenuate that response? We tested whether each of these phases of the host response contributed to threespine sticklebacks’ recently evolved resistance to their tapeworm Schistocephalus solidus. While marine stickleback and some susceptible lake fish permit fast-growing tapeworms, other lake populations are resistant and suppress tapeworm growth via a fibrosis response. We subjected lab-raised fish from three populations (susceptible marine ‘ancestors’, a susceptible lake, a resistant lake), to a novel immune challenge (injection of: 1) a saline control, 2) alum, a generalized pro-inflammatory adjuvant that causes fibrosis, 3) a tapeworm protein extract, and 4) a combination of alum and tapeworm protein). All three populations were capable of a robust fibrosis response to the alum treatments (but not the saline control). Yet, only the resistant population exhibited a fibrosis response to the tapeworm protein alone. Thus, these populations differed in their ability to recognize the tapeworm but shared an intact fibrosis pathway. However, the resistant population also initiated fibrosis faster, and was able to attenuate fibrosis, unlike the susceptible populations slow but longer-lasting response to alum. As fibrosis has presumed pathological side-effects, this difference may reflect adaptions to mitigate costs of immunity in the resistant population. Broadly, our results confirm that parasite detection, activation speed, and immune attenuation simultaneously contribute to adaptations to parasite infection in natural populations.IMPACT SUMMARYDramatic variation in parasite resistance is common in nature, even to the same parasite, yet we are still working to understand the mechanisms of how such differences evolve. Many evolution studies focus on the broad outcomes of infection (infected or not) when studying this question, without specifying what part of the immune response has evolved. Here, we experimentally partition different sequential stages in the host immune response (recognition, actuation, attenuation), to evaluate which stage(s) underly the evolution of host resistance to infection. This study compares three populations of threespine stickleback that naturally differ in their exposure and their ability to resist infections of a freshwater tapeworm. These include a “resistant” lake population, a “susceptible” lake population, and an ancestral marine population that is rarely exposed to the tapeworm in nature, but is susceptible when exposed in the lab. The resistant population exhibits a fibrosis immune response to infection, which has previously been linked to suppressed tapeworm growth and viability. We injected different immune challenges directly into the site of infection (peritoneal cavity) and measured the subsequent fibrosis response through time. We found that all populations were capable of producing fibrosis in response to a general immune stimulant (alum). But, only the resistant population was able to recognize and respond to tapeworm protein alone. This population also responded faster than the others, within 24 hours, and attenuated its fibrosis by 90 days post-injections whereas the other populations exhibited a slower response that did not attenuate in the study time-frame. We concluded that variation in parasite recognition, an early phase in the host response, shapes the evolution of the initiation and resolution of the physical response to infection. Broadly, our results support that parasite detection mechanisms could play a key role in the rapid evolution of parasite resistance.

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Section: Introductionmentioning

confidence: 99%

Rapid Evolution of Parasite Resistance via Improved Recognition and Accelerated Immune Activation and Deactivation

Hund

et al. 2020

Preprint

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“…Consequently, parasite infection reduces host fitness both directly, via effects on survival and reproduction, and indirectly by inducing costly immune responses (Khan et al 2017, Armour et al 2020. Host immunity is adaptive when the benefits of reducing direct effects of infection outweigh the indirect costs of the immune response itself.…”

Section: Introductionmentioning

confidence: 99%

Male and female reproductive fitness costs of an immune response in natural populations

Lisle

Bolnick

2020

Preprint

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Parasites can mediate host fitness both directly, via effects on survival and reproduction, or indirectly by inducing host immune defense with costly side-effects. The evolution of immune defense is determined by a complex interplay of costs and benefits of parasite infection and immune response, all of which may differ for male and female hosts in sexual lineages. Here, we examine fitness costs associated with an inducible immune defense in a fish-cestode host-parasite system. Cestode infection induces peritoneal fibrosis in threespine stickleback (Gasterosteus aculeatus), constraining cestode growth and sometimes encasing and killing the parasite. Surveying two wild populations of stickleback, we confirm that the presence of fibrosis scar tissue is associated with reduced parasite burden in both male and female fish. However, fibrotic fish had lower foraging success and reproductive fitness (reduced female egg production and male nesting success), indicating strong costs of the lingering immunopathology. We show that these substantial sexually-concordant fitness effects of immune response act to align multivariate selection across the sexes, masking the signature of sexual antagonism that acted on morphology alone. Although both sexes experienced costs of fibrosis, the net impacts are unequal because in the two study populations females had higher cestode exposure. To evaluate whether this difference in risk should drive sex-specific immune strategies, we analyze a quantitative genetic model of host immune response to a trophically transmitted parasite. The model and empirical data illustrate how shared costs and benefits of immune response lead to shared evolutionary interests of male and female hosts, despite unequal infection risks across the sexes.

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“… 2017 ; Armour et al. 2020 ). Variation at any of these steps can lead to differences in infection outcomes and immunopathology side effects.…”

mentioning

confidence: 99%

Population-level variation in parasite resistance due to differences in immune initiation and rate of response

et al. 2022

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Closely related populations often differ in resistance to a given parasite, as measured by infection success or failure. Yet, the immunological mechanisms of these evolved differences are rarely specified. Does resistance evolve via changes to the host's ability to recognize that an infection exists, actuate an effective immune response, or attenuate that response? We tested whether each of these phases of the host response contributed to threespine sticklebacks’ recently evolved resistance to their tapeworm Schistocephalus solidus. Although marine stickleback and some susceptible lake fish permit fast‐growing tapeworms, other lake populations are resistant and suppress tapeworm growth via a fibrosis response. We subjected lab‐raised fish from three populations (susceptible marine “ancestors,” a susceptible lake population, and a resistant lake population) to a novel immune challenge using an injection of (1) a saline control, (2) alum, a generalized pro‐inflammatory adjuvant that causes fibrosis, (3) a tapeworm protein extract, or (4) a combination of alum and tapeworm protein. With enough time, all three populations generated a robust fibrosis response to the alum treatments. Yet, only the resistant population exhibited a fibrosis response to the tapeworm protein alone. Thus, these populations differed in their ability to respond to the tapeworm protein but shared an intact fibrosis pathway. The resistant population also initiated fibrosis faster in response to alum, and was able to attenuate fibrosis, unlike the susceptible populations’ slow but longer lasting response to alum. As fibrosis has pathological side effects that reduce fecundity, the faster recovery by the resistant population may reflect an adaptation to mitigate the costs of immunity. Broadly, our results confirm that parasite detection and immune initiation, activation speed, and immune attenuation simultaneously contribute to the evolution of parasite resistance and adaptations to infection in natural populations.

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Low-dose immune challenges result in detectable levels of oxidative damage

Cited by 27 publications

References 83 publications

Rapid Evolution of Parasite Resistance via Improved Recognition and Accelerated Immune Activation and Deactivation

Rapid Evolution of Parasite Resistance via Improved Recognition and Accelerated Immune Activation and Deactivation

Male and female reproductive fitness costs of an immune response in natural populations

Population-level variation in parasite resistance due to differences in immune initiation and rate of response

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