Collateral Damage: Detrimental Effect of Antibiotics on the Development of Protective Immune Memory

Joseph M Benoun, Jasmine C Labuda, Stephen J McSorley, Joseph M Benoun, Jasmine C Labuda, Stephen J McSorley

Abstract

Antibiotic intervention is an effective treatment strategy for many bacterial infections and liberates bacterial antigens and stimulatory products that can induce an inflammatory response. Despite the opportunity for bacterial killing to enhance the development of adaptive immunity, patients treated successfully with antibiotics can suffer from reinfection. Studies in mouse models of Salmonella and Chlamydia infection also demonstrate that early antibiotic intervention reduces host protective immunity to subsequent infection. This heightened susceptibility to reinfection correlates with poor development of Th1 and antibody responses in antibiotic-treated mice but can be overcome by delayed antibiotic intervention, thus suggesting a requirement for sustained T cell stimulation for protection. Although the contribution of memory T cell subsets is imperfectly understood in both of these infection models, a protective role for noncirculating memory cells is suggested by recent studies. Together, these data propose a model where antibiotic treatment specifically interrupts tissue-resident memory T cell formation. Greater understanding of the mechanistic basis of this phenomenon might suggest therapeutic interventions to restore a protective memory response in antibiotic-treated patients, thus reducing the incidence of reinfection.

Copyright © 2016 Benoun et al.

Figures

FIG 1
FIG 1
Antibiotic treatment reduces the development of T cell memory. Primary bacterial infection initiates the expansion of T cells that aid in clearance of the bacteria, leaving a pool of memory T cells behind. Upon secondary infection, these memory cells have acquired effector potential and can eliminate bacteria rapidly. Antibiotic treatment of primary infection truncates T cell expansion and limits memory cell development, preventing an effective response to secondary infection.

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