Functional and phenotypic characteristics of testicular macrophages in experimental autoimmune orchitis

• Published in: The Journal of pathology Vol. 215; no. 2; pp. 108 - 117
• Main Authors: Rival, C, Theas, MS, Suescun, MO, Jacobo, P, Guazzone, V, van Rooijen, N, Lustig, L
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-06-2008; Wiley
• Subjects: Animals; Apoptosis; Autoimmune Diseases - blood; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; autoimmune orchitis; B7-1 Antigen - analysis; B7-2 Antigen - analysis; Biological and medical sciences; Cell Count; Clodronic Acid; costimulatory molecules; cytokines; Cytokines - blood; Flow Cytometry; Follicle Stimulating Hormone - blood; FSH; FSH, LH; Gynecology. Andrology. Obstetrics; Immunoenzyme Techniques; Investigative techniques, diagnostic techniques (general aspects); Luteinizing Hormone - blood; Lymphocyte Activation; Macrophages - immunology; Male; Male genital diseases; Medical sciences; MHC II molecules; Models, Animal; Non tumoral diseases; Orchitis - blood; Orchitis - immunology; Orchitis - pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Rats; Rats, Sprague-Dawley; Spermatozoa - pathology; T-Lymphocytes - immunology; testicular macrophages; Testis - immunology; testosterone; Testosterone - blood; Autoimmunity; testicular macrophages; autoimmune orchitis; MHC II molecules; costimulatory molecules; cytokines; testosterone; FSH; Orchitis; Androgen; Major histocompatibility system; Cytokine; Gonadotropin; Experimental study; Testicle; Male genital system; Costimulatory molecule; Testosterone; Anatomic pathology; Phenotype; Adenohypophyseal hormone; Luteinizing hormone; Testicular hormone; Sex steroid hormone; LH; Male genital diseases; Testicular diseases; Follicle stimulating hormone; Macrophage
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.2328

Testicular inflammation with compromised fertility can occur despite the fact that the testis is considered an immunoprivileged organ. Testicular macrophages have been described as cells with an immunosuppressor profile, thus contributing to the immunoprivilege of the testis. Experimental autoimmune orchitis (EAO) is a model of organ-specific autoimmunity and testicular inflammation. EAO is characterized by an interstitial inflammatory mononuclear cell infiltration, damage of the seminiferous tubules and germ cell apoptosis. Here we studied the phenotype and functions of testicular macrophages during the development of EAO. By stereological analysis, we detected an increased number of resident (ED2⁺) and non-resident (ED1⁺) macrophages in the testicular interstitium of rats with orchitis. We showed that this increase was mainly due to monocyte recruitment. The in vivo administration of liposomes containing clodronate in rats undergoing EAO led to a reduction in the number of testicular macrophages, which correlated with a decreased incidence and severity of the testicular damage and suggests a pathogenic role of macrophages in EAO. By immunohistochemistry and flow cytometry we detected an increased number of testicular macrophages expressing MHC class II, CD80 and CD86 costimulatory molecules in rats with orchitis. Also, testicular macrophages from rats with EAO showed a higher production of IFNγ (ELISA). We conclude that testicular macrophages participate in EAO development, and the ED1⁺ macrophage subset is the main pathogenic subpopulation. They stimulate the immune response through the production of pro-inflammatory cytokines and antigen presentation and thus activation of T cells in the target organ. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.