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It was previously demonstrated that TLR2 and CORO1A (TACO, Coronin 1, p57) localize phagosome membrane of macrophage. However, the functional relationship between TLR2 and CORO1A was not known. We show here that there is a functional counteraction between TLR2 and CORO1A.

Transcription factor, NF-IL6 recognizes the same nucleotide sequences as C/EBP, and it is predominantly expressed in macrophages. Tanaka et al. reported that NF-IL6 knockout mice are highly susceptible to Listeria monocytogenes and Salmonella typhimurium due to impairment of bacteria killing by activated macrophages. We have tried to see the susceptibility for Mycobacterium leprae infection with intraperitoneal(i.p.) or both hind foot pad (BHF) in the NF-IL6 knockout mice with wild control mice. Although we examined the cytokine genes expression and induction of such as IL-1 alpha, IL-6, IL-12, IL-18/IGIF, NO2. and TNF alpha in the peritoneal macrophages on 1 month after inoculation, also IL-2 and IL-10 by splenocytes on 1 and 8 months after infection. Following the inoculation of M. leprae with i.p. or BHF, the mice were sacrificed from 1 to 12 months after inoculation in order to confirm the multiplication and the dissemination of the infection. Many leprosy bacilli was found in the peritoneal macrophages of NF-IL6 knockout mice on 1 month after inoculation while that of the wild control mice was showing disappear. In the case of the intraperitoneal infection, NF-IL6 knockout mice shows predominantly multiplication of M. leprae on the abdemino-organs such as omentum and also scrotum with male. Although NF-IL6 knockout mice with BHF inoculation did not show any swelling at the site of inoculated foot, however the foot pad on 12 month after inoculation was processed for Fite-Faraco's stain and microscopy shows many leprosy bacilli in the intermuscular layer or around the blood vessels/sciatic nerve in the subcutaneous tissue and then the multiplication extended to the toes. Besides the induction of cytokines such as IL-1 alpha, TNF alpha and IL-12 production were observed stronger in culture supernatant of peritoneal macrophages of NF-IL6 knockout mice than that of the wild control mice. IL-2 production was also observed strong in culture supernatant in splenocytes of NF-IL6 knockout mice while that of IL-10 production never induced at anytime. This is doubtless the results of impairment of bacteria killing by macrophages via NF-IL6 gene dependent mechanism not to antigen specific immune system.

Human leukocyte antigens (HLA) were analyzed in Japanese leprosy patients to ascertain whether immunogenetic differences exist between leprosy patients with episcleritis (ES) and those without it. The subjects were 79 Japanese leprosy patients, including 33 patients with a past history of ES, and 49 patients without ES. Controls were 114 healthy subjects. A standard microcytotoxicity test was used for typing HLA-A, -B, -C, -DR and -DQ antigens. HLA-DRB1 and DQB1 genotypings were performed by using the polymerase chain reaction (PCR)-single strand conformation polymorphism and PCR-restriction fragment length polymorphism methods. The occurrence of HLA-Cw3 was significantly greater in the patients with ES (66.7%) than in those without ES (43.5%; odds ratio = 2.6, p < 0.05). The occurrence of HLA-DR4 was significantly lesser in the patients with ES (15.2%) than in those without ES (39.1%; odds ratio = 0.28, p < 0.05) and the controls (46.5%; odds ratio = 0.21, p < 0.005). At the genomic level, the occurrence of HLA-DRB1*0405, DQB1*0401, and DQB1*0302 was significantly lesser in the patients with ES (0%, 0% and 6.1%, respectively) than in those without ES (15.2%, 13.0%, and 26.1%, respectively; odds ratio = 0.07, 0.09 and 0.18, p < 0.05). HLA-DRB1*0405 and DQB1*0401 were also significantly lesser in the patients with ES than in the controls (29.8% and 29.8%; odds ratio = 0.04, p < 0.0001). Our results suggest that HLA-Cw3 causes susceptibility to episcleritis in Japanese patients with leprosy, whereas DR4 (DRB1*0405), DQB1*0401, and DQB1*0302 provide some protection against leprous episcleritis.

Human leukocyte antigens (HLA) class II alleles were analyzed in Japanese leprosy patients to ascertain whether immunogenetic differences exist among the forms of leprosy in classification of World Health Organization-recommended multidrug therapy (WHO-MDT). The subjects were 86 unrelated Japanese leprosy patients, including 62 multibacillary leprosy (MBL), 24 paucibacillary leprosy (PBL). Controls were 114 unrelated healthy subjects. Genotyping of HLA class II alleles was performed by using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and PCR-restriction fragment length polymorphism (RFLP) methods. The frequencies of HLA-DRB1* 1501, * 1502 and DRB5* 0101,* 0102 and DQA1* 0102 and DQB1* 0602 were significantly increased in the whole patients (44.2%, 34.9%, 44.2%, 34.9%, 53.4% and 41.9%, respectively) as compared with the control subjects (14.0%, 21.1%, 14.0%, 21.1%, 27.2% and 13.2%, respectively). On the other hand, the frequencies of HLA-DRB1* 0405, * 0803, * 0901 and DQA1* 03 and DQB1* 0401 were significantly decreased in the whole patients (10.5%, 5.8%, 16.3%, 41.9% and 9.3%, respectively) as compared with the control subjects (29.8%, 17.5%, 30.7%, 78.1% and 29.8%, respectively). When MBL and PBL patients were compared, the frequencies of HLA-DRB1* 1501, DRB5* 0101 and DQB1* 0602 were significantly increased in the MBL patients (51.6%, 51.6% and 48.4%, respectively) as compared with the PBL patients (25.0%, respectively). Our results suggest that HLA-DRB1* 1501, DRB5* 0101 and DQB1* 0602 contribute to the susceptibility to the Japanese MBL.

In order to investigate the role of immunogenetic factors in the pathogenesis of uveitis in leprosy, HLA antigens were analyzed between the leprotics with and without uveitis. Sixty-five Japanese leprosy patients comprised 32 with uveitis and 33 without uveitis. Controls consisted of 138 healthy subjects. A lymphocyte cytotoxicity test was used for typing HLA-A, -B, -C, -DR and -DQ antigens. HLA-DR2 genotyping was performed by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and PCR-restriction fragment length polymorphism (RFLP) methods. The frequency of HLA-DR2 antigen was significantly increased in the patients with uveitis as compared with the control subjects (Pc < 0.0005), whereas HLA-DR53 antigen was significantly decreased (Pc < 0.05). At the genomic level the frequency of HLA-DRB1*1501 was significantly increased in the patients with uveitis and without uveitis as compared with that in the controls. The association with DRB1*1501 was even stronger in patients with uveitis (odds ratio = 7.1, Pc < 0.000005) than in the patients without uveitis (odds ratio = 4.1, Pc < 0.005). Our results suggest that HLA-DRB1*1501 contribute to the susceptibility to uveitis in the Japanese with leprosy.