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Chapter 13 : Single-Cell Metabolism and Stress Responses in Complex Host Tissues

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Abstract:

Infectious diseases are the second most important cause of death worldwide ( ). Public health measures are partially successful in managing infectious disease burden, but major obstacles remain. Efficacious vaccines for major pathogens are still lacking ( ), and the dramatic decline in the development of novel antimicrobials over the last 20 years ( ) together with rapidly rising antimicrobial resistance is substantially reducing treatment options ( ). The emerging crisis in infectious diseases is a major threat to human health.

Citation: Bumann D. 2019. Single-Cell Metabolism and Stress Responses in Complex Host Tissues, p 179-196. In Cossart P, Roy C, Sansonetti P (ed), Bacteria and Intracellularity. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.BAI-0009-2019
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Figure 1

A paradigm shift in pathogen analysis in host tissues. () Common methods relied on population-level readouts that revealed average properties. This revealed many exciting insights, including identification of important vaccine antigens and antimicrobial targets. () Single-cell technologies reveal an additional striking heterogeneity of pathogen properties and fates that range from vigorous growth to efficient killing. All these diverse host-pathogen encounters can occur in the same host tissue at the same time. Overall disease outcome is the net result of this underlying complexity. Identifying the molecular mechanisms that distinguish successful (for the host) from failing encounters could provide a basis for entirely novel strategies in infection control, by broadening successful host antimicrobial attacks and closing permissive niches in which pathogen subsets can thrive.

Citation: Bumann D. 2019. Single-Cell Metabolism and Stress Responses in Complex Host Tissues, p 179-196. In Cossart P, Roy C, Sansonetti P (ed), Bacteria and Intracellularity. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.BAI-0009-2019
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Figure 2

Working model for -host interactions in an infected spleen. () interactions with various phagocyte types. proliferates in macrophages (MΦ) and spreads to other cells. When entering a macrophage, a cell is exposed to a short and sublethal oxidative burst. Infiltrating NK and T cells secrete IFN-γ, which activates some macrophages, enabling them to kill intracellular salmonellae in part through guanylate-binding protein 2 (GBP2). Infection foci also attract inflammatory monocytes (iMO) and polymorphonuclear neutrophils (PMN), which kill intracellular with hypochlorite (HOCl; bleach). Inflammatory monocytes generate and release large amounts of NO, which diffuses to regional salmonellae, which in turn upregulate detoxifying and damage repair enzymes. () Lesion formation and spreading in infected tissues. Growing infection foci attract inflammatory monocytes (blue) and neutrophils (magenta) that kill many . However, some salmonellae escape in infected macrophages (cyan) and start new infection foci elsewhere. Early infection foci are detected by NK and T cells (green), which secrete IFN-γ and activate some of the local macrophages. Other macrophages move to yet other tissue regions, thereby spreading the infection and driving disease progression.

Citation: Bumann D. 2019. Single-Cell Metabolism and Stress Responses in Complex Host Tissues, p 179-196. In Cossart P, Roy C, Sansonetti P (ed), Bacteria and Intracellularity. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.BAI-0009-2019
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