A dynamical motif comprising the interactions between antigens and CD8 T cells may underlie the outcomes of viral infections

Baral, Subhasish and Antia, Rustom and Dixit, Narendra M (2019) A dynamical motif comprising the interactions between antigens and CD8 T cells may underlie the outcomes of viral infections. In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 116 (35). pp. 17393-17398.

Preview	PDF PRO_THE_NAT_ACA_SCI_USA_116-35_17393_2019.pdf - Published Version Download (1MB) | Preview
Preview	PDF pnas.1902178116.sapp.pdf - Published Supplemental Material Download (2MB) | Preview
Preview	Image (JPEG) F1.large (1).jpg - Published Supplemental Material Download (176kB) | Preview
Preview	Image (JPEG) F2.large.jpg - Published Supplemental Material Download (160kB) | Preview
Preview	Image (JPEG) F3.large.jpg - Published Supplemental Material Download (156kB) | Preview
Preview	Image (JPEG) F4.large.jpg - Published Supplemental Material Download (80kB) | Preview
Preview	Image (JPEG) F5.large.jpg - Published Supplemental Material Download (115kB) | Preview

Abstract

Some viral infections culminate in very different outcomes in different individuals. They can be rapidly cleared in some, cause persistent infection in others, and cause mortality from immunopathology in yet others. The conventional view is that the different outcomes arise as a consequence of the complex interactions between a large number of different factors (virus, different immune cells, and cytokines). Here, we identify a simple dynamical motif comprising the essential interactions between antigens and CD8 T cells and posit it as predominantly determining the outcomes. Viral antigen can activate CD8 T cells, which in turn, can kill infected cells. Sustained antigen stimulation, however, can cause CD8 T-cell exhaustion, compromising effector function. Using mathematical modeling, we show that the motif comprising these interactions recapitulates all of the outcomes observed. The motif presents a conceptual framework to understand the variable outcomes of infection. It also explains a number of confounding experimental observations, including the variation in outcomes with the viral inoculum size, the evolutionary advantage of exhaustion in preventing lethal pathology, the ability of natural killer (NK) cells to act as rheostats tuning outcomes, and the role of the innate immune response in the spontaneous clearance of hepatitis C. Interventions that modulate the interactions in the motif may present routes to clear persistent infections or limit immunopathology.

Item Type:	Journal Article
Publication:	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publisher:	NATL ACAD SCIENCES
Additional Information:	Copy right to this article belongs to NATL ACAD SCIENCES
Keywords:	acute infection; chronic infection; immunopathology; mathematical model; bistability
Department/Centre:	Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering Division of Mechanical Sciences > Chemical Engineering
Date Deposited:	23 Sep 2019 06:28
Last Modified:	23 Sep 2019 06:28
URI:	http://eprints.iisc.ac.in/id/eprint/63595

Actions (login required)

View Item