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 5

Oxylipin 10-HOME polarizes naive CD4+ T cells to Th1 subtype in vitro.

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Oxylipin 10-HOME polarizes naive CD4+ T cells to Th1 subtype in vitro. (...
(A) Increased expression of CD36 in naive CD4+ T cells treated with 10-HOME immunostained with anti-CD4 (red), anti-CD36 (green), and DAPI (blue). We quantified the fluorescent intensity of CD36. Colocalization of CD4 and CD36 depicted increased abundance of CD4+ CD36+ cells. Data presented as mean ± SD, (n = 6). Scale bar: 10 μm. A t test was used to determine vehicle versus 10-HOME, intensity (P < 0.0001), colocalization (P < 0.0001). (B) We found elevated CD36 in the 10-HOME treated naive T cells. Flow cytometry analyses of treated cells stained with anti-CD4 (FITC) and anti-CD36 (APC). Representative plots: vehicle, 10-HOME-treated cells, histograms with isotype control for CD36. Data presented as mean ± SD, (n = 7). t test was used to determine vehicle versus 10-HOME(P = 0.0044). (C) Increased expression of T-BET in the 10-HOME–treated naive CD4+ T cells immunostained with anti-CD4 (red), anti-TBET (green), and DAPI (blue). We quantified the fluorescent intensity of TBET. Colocalization of CD4 and TBET depicted increased abundance of CD4+ TBET+ cells. Data presented as mean ± SD, (n = 6). Scale bar: 10 μm. A t test was used to determine vehicle versus 10-HOME intensity (P = 0.0094) and colocalization(P = 0.0012). (D) Elevated Th1 subtype (CD183+) in the 10-HOME–treated naive CD4+ T cells. Flow cytometry analyses with anti-CD4 (FITC) and anti-CD183 (PE). Representative plots: vehicle-treated, 10-HOME–treated cells, and histograms of cells with isotype control for CD183. Data presented as mean ± SD, (n = 7). t test was used to determine vehicle versus 10-HOME Intensity (P = 0.0094) and colocalization (P = 0.0003). (E) Increased expression of IFN-γ in the 10-HOME–treated naive CD4+ T cells as measured through ELISA. Data presented as mean ± SD (n = 7). t test was used to determine vehicle versus 10-HOME Intensity (P = 0.0094), colocalization(P < 0.0001). (F and G) There was no significant change in IL4 and IL10 following 10-HOME treatment of naive CD4+ T cells. Data presented as mean ± SD, (n = 8). t test was used to determine vehicle versus 10-HOME, 1L4 (P = 0.1564), IL10 (P = 0.1085). (H and I) Increased expression of (H) CD36 and (I) T-BET in 10-HOME–treated naive T cells. Data presented as mean ± SD, (n = 6). t test was used to determine vehicle versus 10-HOME CD36 (P = 0.0027) and T-BET (P = 0.0004).