TY - JOUR
T1 - Protection Generated by Prior Exposure to Pathogens Depends on both Priming and Challenge Dose
AU - Weitzman, Chava L.
AU - Ceja, Guadalupe
AU - Leon, Ariel E.
AU - Hawley, Dana M.
N1 - Funding Information:
This work was supported by National Science Foundation grant IOS-1755051. Research reported in this publication was also partly supported by the National Institute of General Medical Sciences of the National Institutes of Health (NIH) under award number R01GM144972. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. G.C. was supported by the Virginia Tech Postbaccalaureate Research and Education Program, NIH.
Publisher Copyright:
Copyright © 2022 American Society for Microbiology. All Rights Reserved.
PY - 2022/3
Y1 - 2022/3
N2 - Free-living hosts encounter pathogens at a wide range of frequencies and concentrations, including low doses that are largely aclinical, creating a varied landscape of exposure history and reinfection likelihood. While several studies show that higher priming doses result in stronger immunological protection against reinfection, it remains unknown how the reinfection challenge dose and priming dose interact to determine the likelihood and severity of reinfection. We manipulated both priming and challenge doses of Mycoplasma gallisepticum, which causes mycoplasmal conjunctivitis, in captive house finches (Haemorhous mexicanus), to assess reinfection probability and severity. We found a significant interaction between priming and challenge doses on reinfection probability, with the likelihood of reinfection by a high but not a low challenge dose decreasing exponentially at higher priming doses. While this interaction was likely driven by lower average infection probabilities for low-dose versus high-dose challenges, even the highest priming dose provided only negligible protection against reinfection from low-dose challenges. Similarly, pathogen loads during reinfection were significantly reduced with increasing priming doses only for birds reinfected at high but not low doses. We hypothesize that these interactions arise to some degree from fundamental differences in host immune responses across doses, with single low doses only weakly triggering host immune responses. Importantly, our results also demonstrate that reinfections can occur from a variety of exposure doses and across diverse degrees of standing immunity in this system. Overall, our study highlights the importance of considering both initial and subsequent exposure doses where repeated exposure to a pathogen is common in nature.
AB - Free-living hosts encounter pathogens at a wide range of frequencies and concentrations, including low doses that are largely aclinical, creating a varied landscape of exposure history and reinfection likelihood. While several studies show that higher priming doses result in stronger immunological protection against reinfection, it remains unknown how the reinfection challenge dose and priming dose interact to determine the likelihood and severity of reinfection. We manipulated both priming and challenge doses of Mycoplasma gallisepticum, which causes mycoplasmal conjunctivitis, in captive house finches (Haemorhous mexicanus), to assess reinfection probability and severity. We found a significant interaction between priming and challenge doses on reinfection probability, with the likelihood of reinfection by a high but not a low challenge dose decreasing exponentially at higher priming doses. While this interaction was likely driven by lower average infection probabilities for low-dose versus high-dose challenges, even the highest priming dose provided only negligible protection against reinfection from low-dose challenges. Similarly, pathogen loads during reinfection were significantly reduced with increasing priming doses only for birds reinfected at high but not low doses. We hypothesize that these interactions arise to some degree from fundamental differences in host immune responses across doses, with single low doses only weakly triggering host immune responses. Importantly, our results also demonstrate that reinfections can occur from a variety of exposure doses and across diverse degrees of standing immunity in this system. Overall, our study highlights the importance of considering both initial and subsequent exposure doses where repeated exposure to a pathogen is common in nature.
KW - House finch
KW - Immunological protection
KW - Mycoplasma gallisepticum
KW - Mycoplasmal conjunctivitis
KW - Reinfection
UR - http://www.scopus.com/inward/record.url?scp=85126909638&partnerID=8YFLogxK
U2 - 10.1128/iai.00537-21
DO - 10.1128/iai.00537-21
M3 - Article
C2 - 35041488
AN - SCOPUS:85126909638
VL - 90
SP - 1
EP - 10
JO - Infection and Immunity
JF - Infection and Immunity
SN - 0019-9567
IS - 3
M1 - e00537-21
ER -