Biofilm-derived oxylipin 10-HOME–mediated immune response in women with breast implants
Imran Khan, … , Marshall E. Kadin, Mithun Sinha
Imran Khan, … , Marshall E. Kadin, Mithun Sinha
Published November 30, 2023
Citation Information: J Clin Invest. 2024;134(3):e165644. https://doi.org/10.1172/JCI165644.
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Research Article Immunology Inflammation

Biofilm-derived oxylipin 10-HOME–mediated immune response in women with breast implants

Abstract

This study investigates a mechanistic link of bacterial biofilm–mediated host-pathogen interaction leading to immunological complications associated with breast implant illness (BII). Over 10 million women worldwide have breast implants. In recent years, women have described a constellation of immunological symptoms believed to be related to their breast implants. We report that periprosthetic breast tissue of participants with symptoms associated with BII had increased abundance of biofilm and biofilm-derived oxylipin 10-HOME compared with participants with implants who are without symptoms (non-BII) and participants without implants. S. epidermidis biofilm was observed to be higher in the BII group compared with the non-BII group and the normal tissue group. Oxylipin 10-HOME was found to be immunogenically capable of polarizing naive CD4+ T cells with a resulting Th1 subtype in vitro and in vivo. Consistently, an abundance of CD4+Th1 subtype was observed in the periprosthetic breast tissue and blood of people in the BII group. Mice injected with 10-HOME also had increased Th1 subtype in their blood, akin to patients with BII, and demonstrated fatigue-like symptoms. The identification of an oxylipin-mediated mechanism of immune activation induced by local bacterial biofilm provides insight into the possible pathogenesis of the implant-associated immune symptoms of BII.

Authors

Imran Khan, Robert E. Minto, Christine Kelley-Patteson, Kanhaiya Singh, Lava Timsina, Lily J. Suh, Ethan Rinne, Bruce W. Van Natta, Colby R. Neumann, Ganesh Mohan, Mary Lester, R. Jason VonDerHaar, Rana German, Natascia Marino, Aladdin H. Hassanein, Gayle M. Gordillo, Mark H. Kaplan, Chandan K. Sen, Marshall E. Kadin, Mithun Sinha

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Figure 6

Elevated CD4+ Th1 and fatigue-like symptoms in mice administered with 10-HOME.

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Elevated CD4+ Th1 and fatigue-like symptoms in mice administered with 10...
(A) Schematic representation of injection of 10-HOME in the abdominal mammary fat pad of mice. (B) Timeline of 10-HOME administration in mice. (C) Elevated CD4+ Th1 subtype in the blood of mice injected with 10-HOME. Flow cytometry analyses of blood of mice stained with anti-CD4 (FITC) and anti-CD183 (PE). Representative flow plots: vehicle-treated, 10-HOME-treated, and histograms with isotype control for CD183. Data presented as mean ± SEM, vehicle (n = 9) and 10-HOME (n = 9) –treated mice. Wilcoxon-Rank test analysis was used to determine vehicle versus 10-HOME (P < 0.001). (D) Elevated CD4+ Th1 subtype in the blood of mice injected with 10-HOME. Flow cytometry analyses of blood of mice stained with anti-CD4 (FITC) and anti-Tbet (PE). Representative flow plots: vehicle-treated and 10-HOME–treated histograms with isotype control for T-bet. Data presented as mean ± SEM, vehicle (n = 6) and 10-HOME (n = 6) mice. t test was used to determine vehicle versus 10-HOME (P = 0.0459). (E) Unaltered CD4+ Th2 subtype in the blood of mice injected with 10-HOME. Flow cytometry analyses of blood of mice stained with anti-CD4 (FITC) and anti-CD194 (PE). Representative flow plots: vehicle-treated and 10-HOME–treated histograms with isotype control for CD194. Data presented as mean ± SEM, vehicle (n = 6) and 10-HOME (n = 8) –treated mice. t test was used to determine vehicle versus 10-HOME (P = 0.6999). (F) Representative image of murine endurance test after 10-HOME administration. Video provided as Supplemental Video 1. (G) Increased stops exhibited by 10-HOME administered mice compared with those treated with vehicle. Data presented as mean ± SEM, vehicle (n = 6) and 10-HOME (n = 5) –treated mice. Mann-Whitney U test with a Bonferroni correction was performed (P = 0.0087). (H) Increased aversive stimulation (shock grid touching) exhibited by mice administered 10-HOME compared with those treated with vehicle. Data presented as mean ± SEM, vehicle (n = 6) and 10-HOME (n = 5) –treated mice. Mann-Whitney U test with a Bonferroni correction was performed (P = 0.0065).