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

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

doi:10.1128/mbio.01520-16

Cited by 30 publications

(21 citation statements)

References 81 publications

(107 reference statements)

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“…Intracellular pathogens like Salmonella cause high disease mortality and morbidity worldwide (3,41). Next-generation Vi capsular polysaccharide-conjugate typhoid vaccines are likely to enhance protection against Vi-expressing typhoid serovars, but will not combat systemic salmonellosis caused by Vi-negative paratyphoid or nontyphoidal serovars (42,43).…”

Section: Discussionmentioning

confidence: 99%

Optimal protection againstSalmonellainfection requires noncirculating memory

Benoun

Peres

Wang

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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While CD4 Th1 cells are required for resistance to intramacrophage infections, adoptive transfer of Th1 cells is insufficient to protect against Salmonella infection. Using an epitope-tagged vaccine strain of Salmonella, we found that effective protection correlated with expanded Salmonella-specific memory CD4 T cells in circulation and nonlymphoid tissues. However, naive mice that previously shared a blood supply with vaccinated partners lacked T cell memory with characteristics of tissue residence and did not acquire robust protective immunity. Using a YFP–IFN-γ reporter system, we identified Th1 cells in the liver of immunized mice that displayed markers of tissue residence, including P2X7, ARTC2, LFA-1, and CD101. Adoptive transfer of liver memory cells after ARTC2 blockade increased protection against highly virulent bacteria. Taken together, these data demonstrate that noncirculating memory Th1 cells are a vital component of immunity to Salmonella infection and should be the focus of vaccine strategies.

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Section: Discussionmentioning

confidence: 99%

Optimal protection againstSalmonellainfection requires noncirculating memory

Benoun

Peres

Wang

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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“…(ii) Patients have history of other malignancies, or they have been previously treated with any anti-cancer agents, non-steroid antiinflammatory drugs (NSAIDs), or antibiotics. An infectious or inflammatory status, or the administration of specific agents to intervene such conditions would affect the accuracy of blood test, so patients with any record of these conditions mentioned above were excluded from this study [34][35][36][37]. (iii) Patients with incomplete medical records or laboratory results were also excluded.…”

Section: Patient Selectionmentioning

confidence: 99%

Prognostic value of pre-treatment Naples prognostic score (NPS) in patients with osteosarcoma

et al. 2020

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Background: This study aimed to evaluate the clinical significance of pre-treatment Naples prognostic score (NPS) in patients with osteosarcoma. Methods: The clinical data of 133 osteosarcoma patients between January 2011 and February 2018 in our hospital was retrospectively collected and analyzed. NPS was calculated from four parameters, including serum albumin level, serum total cholesterol (TC), lymphocyte-to-monocyte ratio (LMR), and neutrophil-to-lymphocyte ratio (NLR). Patients were divided into three groups (group 1-3) based on NPS. The relationships between NPS and clinical features, overall survival (OS), and progression-free survival (PFS) were analyzed. Two prediction models based on NPS and clinical parameters were developed: clinical parameters model (model A), and the combined model of NPS and clinical parameters (model B). Their predictive performances were further evaluated and compared. Results: The median follow-up time of this cohort was 46.0 (range, 5-75) months, while the median OS and PFS was 40 (range, 5-75) months and 36 (range, 5-71) months, respectively. NPS was significantly correlated with gender, tumor location, Enneking stage, pathological fracture, local recurrence, and metastasis (all P < 0.05). Variables of NPS, Enneking stage, local recurrence, metastasis, and NLR were confirmed as independent prognostic factors for OS and PFS by univariate and multivariate Cox analysis. Prediction model B obtained larger AUCs for OS and PFS and showed better consistency between nomogram-predicted and actual survival than that of model A at the follow-up time of 1-, 3-, and 5-year. Conclusions: NPS was a novel, reliable, and multidimensional prognostic scoring system with favorable predictive performance for patients with osteosarcoma.

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“…On the other hand, while early-life immune development has consequences that play out well into adulthood (32), antibiotic use in adulthood also may jeopardize protective responses to infectious agents (33). Benoun et al (33) have suggested that the therapeutic use of antibiotics may impair the formation of tissue-resident CD4 memory T cells by shortening the period of antigen presentation. Also, as we discuss later, antibiotics may have detrimental effects on vaccine responses (34).…”

Section: Microbiome and Immune System Developmentmentioning

confidence: 99%

Microbiome as a tool and a target in the effort to address antimicrobial resistance

Relman

Lipsitch

2018

Proc. Natl. Acad. Sci. U.S.A.

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Reciprocal, intimate relationships between the human microbiome and the host immune system are shaped by past microbial encounters and prepare the host for future ones. Antibiotics and other antimicrobials leave their mark on both the microbiome and host immunity. Antimicrobials alter the structure of the microbiota, expand the host-specific pool of antimicrobial-resistance genes and organisms, degrade the protective effects of the microbiota against invasion by pathogens, and may impair vaccine efficacy. Through these effects on the microbiome they may affect immune responses. Vaccines that exert protective or therapeutic effects against pathogens may reduce the use of antimicrobials, the development and spread of antimicrobial resistance, and the harmful impacts of these drugs on the microbiome. Other strategies involving manipulation of the microbiome to deplete antibiotic-resistant organisms or to enhance immune responses to vaccines may prove valuable in addressing antimicrobial resistance as well. This article describes the intersections of immunity, microbiome and antimicrobial exposure, and the use of vaccines and other alternative strategies for the control and management of antimicrobial resistance.

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

Cited by 30 publications

References 81 publications

Optimal protection againstSalmonellainfection requires noncirculating memory

Optimal protection againstSalmonellainfection requires noncirculating memory

Prognostic value of pre-treatment Naples prognostic score (NPS) in patients with osteosarcoma

Microbiome as a tool and a target in the effort to address antimicrobial resistance

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