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Synopsis Immunopathology, or the harm caused to an organism’s own tissues during the activation of its immune system, carries substantial costs. Moreover, avoiding this self-harm may be an important mechanism underlying tolerance of infection, helping to reducing fitness costs without necessarily clearing parasites. Despite the apparent benefits of minimizing immunopathology, such damage persists across a range of host species. Prior work has explored a trade-off with resistance during a single infection as a potential driver of this persistence, with some collateral damage being unavoidable when killing parasites. Here, we present an additional trade-off that could favor the continued presence of immunopathology: robust immune responses during initial infection (e.g., innate immunity in vertebrates) can induce stronger memory (adaptive immunity), offering protection from future infections. We explore this possibility in an adaptive dynamics framework, using theoretical models parameterized from an ecologically relevant host-parasite system, house finches (Haemorhous mexicanus) infected with the bacterial pathogen, Mycoplasma gallisepticum. We find that some degree of immunopathology is often favored when immunopathology during first infection either reduces susceptibility to or enhances recovery from second infection. Further, interactions among factors like transmission rate, recovery rate, background mortality, and pathogen virulence also shape these evolutionary dynamics. Most notably, the evolutionary stability of investment in immunopathology is highly dependent upon the mechanism by which hosts achieve secondary protection (susceptibility vs. recovery), with the potential for abrupt evolutionary shifts between high and low investment under certain conditions. These results highlight the potential for immune memory to play an important role in the evolutionary persistence of immunopathology and the need for future empirical research to reveal the links between immunopathology during initial infections and longer-term immune protection.
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Varying conjunctival immune response adaptations of house finch populations to a rapidly evolving bacterial pathogen
Pathogen adaptations during host-pathogen co-evolution can cause the host balance between immunity and immunopathology to rapidly shift. However, little is known in natural disease systems about the immunological pathways optimised through the trade-off between immunity and self-damage. The evolutionary interaction between the conjunctival bacterial infectionMycoplasma gallisepticum(MG) and its avian host, the house finch (Haemorhous mexicanus), can provide insights into such adaptations in immune regulation. Here we use experimental infections to reveal immune variation in conjunctival tissue for house finches captured from four distinct populations differing in the length of their co-evolutionary histories with MG and their disease tolerance (defined as disease severity per pathogen load) in controlled infection studies. To differentiate contributions of host versus pathogen evolution, we compared house finch responses to one of two MG isolates: the original VA1994 isolate and a more evolutionarily derived one, VA2013. To identify differential gene expression involved in initiation of the immune response to MG, we performed 3’-end transcriptomic sequencing (QuantSeq) of samples from the infection site, conjunctiva, collected 3-days post-infection. In response to MG, we observed an increase in general pro-inflammatory signalling, as well as T-cell activation and IL17 pathway differentiation, associated with a decrease in the IL12/IL23 pathway signalling. The immune response was stronger in response to the evolutionarily derived MG isolate compared to the original one, consistent with known increases in MG virulence over time. The host populations differed namely in pre-activation immune gene expression, suggesting population-specific adaptations. Compared to other populations, finches from Virginia, which have the longest co-evolutionary history with MG, showed significantly higher expression of anti-inflammatory genes and Th1 mediators. This may explain the evolution of disease tolerance to MG infection in VA birds. We also show a potential modulating role of BCL10, a positive B- and T-cell regulator activating the NFKB signalling. Our results illuminate potential mechanisms of house finch adaptation to MG-induced immunopathology, contributing to understanding of the host evolutionary responses to pathogen-driven shifts in immunity-immunopathology trade-offs.
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- Award ID(s):
- 1754872
- PAR ID:
- 10507125
- Publisher / Repository:
- NSF-PAR
- Date Published:
- Journal Name:
- Frontiers in Immunology
- Volume:
- 15
- ISSN:
- 1664-3224
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3389/fimmu.2024.1250818
