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\begin{document}

\title{Pathogen interactions with host resources and immunity result in bimodal
infection outcomes}



\author[1]{Guozhi Yu}%
\author[2]{Yingying Hu}%
\author[3]{Shizhong Wang}%
\author[1]{Xinfa Han}%
\author[1]{Xiaogang Du}%
\author[1]{Huailiang Xu}%
\author[1]{Xianyin Zeng}%
\author[4]{Ulrich Steiner}%
\author[5]{Jens Rolff}%
\affil[1]{Sichuan Agricultural University}%
\affil[2]{College of Life Science, Sichuan Agricultural University}%
\affil[3]{Affiliation not available}%
\affil[4]{Freie Universität Berlin}%
\affil[5]{Free University of Berlin}%


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  \date{June 17, 2024}


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\begin{abstract}
Death or survival are the two outcomes of an infection. Pathogen
infections perturb the resource and energy balance of hosts and in
response hosts adjust metabolism and resource assimilation. Host
resistance against infection relies on the allocation of resources, in
particular to mount sufficient immune responses. We hypothesize that
interactions between host resources, host immune responses and pathogens
determine host homeostasis and result in contrasting infection outcomes.
In this study, we mathematically formulate these interactions and find
that the temporal dynamics lead to two distinct trajectories of disease
progression. The pathogen load responds in a bistable manner by either
proliferating or persisting, if not being eliminated, which corresponds
to the death or survival of the host. We identified two key negative
feedbacks causing bistability: 1) host resources are either directly
consumed or indirectly inhibited by pathogens; 2) pathogen elimination
by the host immune response. The dynamics is also sensitive to ``initial
conditions'', such as resource availability, immunocompetence, and
pathogen load at the onset of infection. Our result provides a
mechanistic intuitive explanation for the bistable outcome of pathogen
infection based on resource reallocation. It also provides a
quantitative framework to monitor disease trajectories and forecast the
physiological tipping point of death and survival.%
\end{abstract}%



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\textbf{Hosted file}

\verb`maintext-H-P-EL - \begin{CJK}{UTF8}{gbsn}副本.\end{CJK}\selectlanguage{english}docx`  available at \url{https://authorea.com/users/738818/articles/712846-pathogen-interactions-with-host-resources-and-immunity-result-in-bimodal-infection-outcomes}

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