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Reduced parasitic infection rates in the developed world are suspected to underlie the rising prevalence of autoimmune disorders. However, the long-term evolutionary consequences of decreased parasite exposure on an immune system are not well understood. We used the Mexican tetra Astyanax mexicanus to understand how loss of parasite diversity influences the evolutionary trajectory of the vertebrate immune system, by comparing river with cave morphotypes. Here, we present field data affirming a strong reduction in parasite diversity in the cave ecosystem, and show that cavefish immune cells display a more sensitive pro-inflammatory response towards bacterial endotoxins. Surprisingly, other innate cellular immune responses, such as phagocytosis, are drastically decreased in cavefish. Using two independent single-cell approaches, we identified a shift in the overall immune cell composition in cavefish as the underlying cellular mechanism, indicating strong differences in the immune investment strategy. While surface fish invest evenly into the innate and adaptive immune systems, cavefish shifted immune investment to the adaptive immune system, and here, mainly towards specific T-cell populations that promote homeostasis. Additionally, inflammatory responses and immunopathological phenotypes in visceral adipose tissue are drastically reduced in cavefish. Our data indicate that long-term adaptation to low parasite diversity coincides with a more sensitive immune system in cavefish, which is accompanied by a reduction in the immune cells that play a role in mediating the pro-inflammatory response.
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A MATHEMATICAL STUDY OF THE IMPLICIT ROLE OF INNATE AND ADAPTIVE IMMUNE RESPONSES ON WITHIN-HUMAN PLASMODIUM FALCIPARUM PARASITE LEVELS
A within-human-host malaria parasite model, integrating key variables that influence parasite evolution-progression-advancement, under innate and adaptive immune responses, is analyzed. The implicit role of immunity on the steady state parasite loads and parasitemia reproduction number ([Formula: see text]), a threshold parameter measuring the parasite’s annexing ability of healthy red blood cells (HRBCs), eventually rendering a human infectious to mosquitoes, is investigated. The impact of the type of recruitment function used to model HRBC growth is also investigated. The model steady states and [Formula: see text], both obtained as functions of immune system variables, are analyzed at snapshots of immune sizes. Model results indicate that the more the immune cells, innate and adaptive, the more efficient they are at inhibiting parasite development and progression; consequently, the less severe the malaria disease in a patient. Our analysis also illustrates the existence of a Hopf bifurcation leading to a limit cycle, observable only for the nonlinear recruitment functions, at reasonably large [Formula: see text].
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- Award ID(s):
- 1815912
- PAR ID:
- 10192478
- Date Published:
- Journal Name:
- Journal of Biological Systems
- Volume:
- 28
- Issue:
- 02
- ISSN:
- 0218-3390
- Page Range / eLocation ID:
- 377 to 429
- 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/10.1142/S0218339020400069
