Abstract
1 Comparative Immunogenetics Laboratory, Texas A&M University, College Station, Texas, United States of America, 2 Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America, 3 Department of Plant Pathology and Microbiology, College of Agriculture and Life Sciences, Texas A&M University, College Station, Texas, United States of America, 4 Norman Borlaug Center, Texas A&M University, College Station, Texas, United States of America, 5 Department of Microbial and Molecular Pathogenesis, College of Medicine, Texas A&M Health Science Center, College Station, Texas, United States of America
Highlights
We suggest that the cellular physiology of this pathway has evolved from functioning in recycling of cellular debris and tissue remodeling in early eukaryotes [46], to functioning primarily for nutritional purposes in heterotrophic protozoa, on to the killing of pathogens in innate immunity [55], and to elegant regulation of adaptive immunity via antigen processing [56] (Figure 3)
Just as pH is a fundamental property of living systems, acid is employed by both host and pathogen in their ever-escalating arms race
On the side of the host, acid is used in a variety of mechanisms, including extracellular innate immunity at mucosal surfaces and extreme pH in the case of the mammalian stomach
Summary
Cells and organisms are largely aqueous entities and have evolved sophisticated strategies for sensing, exploiting, and modifying the pH of their surrounding environments for assorted biological processes, including nutrient acquisition, intercellular communication, virulence, and defense against invading pathogens. Cells generate and exploit biological acids for essential functions, including the denaturation of proteins destined for degradation and the activation of acid hydrolases that mediate this process [3], and as potent activators of intracellular signaling events [4,5,6,7]. We focus on how biological acids are generated, exploited, and manipulated by hosts and pathogens during infection and disease progression. We conclude by comparing broad themes that bridge or separate the mechanisms by which evolutionarily divergent pathogens and hosts evade, subvert, or exploit biological acids
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