Biofilm-derived oxylipin 10-HOME–mediated immune response in women with breast implants
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
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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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 3

Comparative transcriptomic and molecular pathway analyses of participants with BII.

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Comparative transcriptomic and molecular pathway analyses of participant...
(A) Hierarchical clustering of genes with at least 2-fold change and controlled by FDR of 0.05 breast tissue from participants in the normal (n = 34), non-BII (n = 16), and BII (n = 24) groups. (B) Gene interaction networks for functions related to differentiation of T-lymphocytes, differentiation of Th1 cells, cell proliferation of T-lymphocytes, maturation of T-lymphocytes, generation of T-helper lymphocytes, differentiation of helper T-lymphocytes, T cell response, T cell development, and quantity of T-lymphocytes in BII specimens. Represented functional networks relevant to the set of imported genes generated by the canonical pathway function relevant to Th1 pathway. The list was selected from the hierarchical cluster of Th1 genes; upregulated genes are shown in red and downregulated in green. The intensity of red and green corresponds to an increase and decrease, respectively, in log2 fold change. (C) Comparison of normalized RNA-Seq counts for CD36 between samples from normal, non-BII, and BII groups. In an age-adjusted nonparametric regression model, compared with participants in the normal group, normalized number of CD36 counts was approximately 1,116 units higher in the BII group (P < 0.0001) and 650 units higher in the non-BII group (P < 0.0001). (D) Comparison of normalized RNA-Seq counts for Th1 gene T-BET (TBX21) between normal, non-BII, and BII samples. In an age-adjusted nonparametric regression model, compared with participants in the normal group, the normalized number of T-BET counts was approximately 18 units higher in the BII group (P = 0.005) and 11 units higher in the non-BII group (P = 0.011). (E) Comparison of normalized RNA-Seq counts for Th1 gene IL12RB2 between normal, non-BII, and BII samples. In an age-adjusted nonparametric regression model, compared with participants in the normal group, the normalized number of IL12RB2 counts was approximately 84 units higher in the BII group (P < 0.0001) and 45 units higher in the non-BII group (P < 0.0001).