Characterization of the HHV-6B U20 Immunoevasin.

Roseoloviruses (human herpesvirus 6A [HHV-6A], -6B, and -7) infect >90% of the human population during early childhood and are thought to remain latent or persistent throughout the life of the host. As such, these viruses are among the most pervasive and stealthy of all viruses; they must necessarily excel at escaping immune detection throughout the life of the host, and yet, very little is known about how these viruses so successfully escape host defenses. Here, we characterize the expression, trafficking, and posttranslational modifications of the HHV6B U20 gene product, which is encoded within a block of genes unique to the roseoloviruses. HHV-6B U20 trafficked slowly through the secretory system, receiving several posttranslational modifications to its N-linked glycans, indicative of surface-expressed glycoproteins, and eventually reaching the cell surface before being internalized. Interestingly, U20 is also phosphorylated on at least one Ser, Thr, or Tyr residue. These results provide a framework to understand the role(s) of U20 in evading host defenses. IMPORTANCE The roseolovirus U20 proteins are virus-encoded integral membrane glycoproteins possessing class I major histocompatibility complex (MHC)-like folds. Surprisingly, although U20 proteins from HHV-6A and -6B share 92% identity, recent studies ascribe different functions to HHV6A U20 and HHV6B U20. HHV6A U20 was shown to downregulate NKG2D ligands, while HHV6B U20 was shown to inhibit tumor necrosis factor alpha (TNF-α)-induced apoptosis during nonproductive infection with HHV6B (E. Kofod-Olsen, K. Ross-Hansen, M. H. Schleimann, D. K. Jensen, et al., J Virol 86:11483-11492, 2012, https://doi.org/10.1128/jvi.00847-12; A. E. Chaouat, B. Seliger, O. Mandelboim, D. Schmiedel, Front Immunol 12:714799, 2021, https://doi.org/10.3389/fimmu.2021.714799). Here, we have performed cell biological and biochemical characterization of the trafficking, glycosylation, and posttranslational modifications occurring on HHV6B U20.

CD38+ M-MDSC expansion characterizes a subset of advanced colorectal cancer patients.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are a population of immature immune cells with several protumorigenic functions. CD38 is a transmembrane receptor-ectoenzyme expressed by MDSCs in murine models of esophageal cancer. We hypothesized that CD38 could be expressed on MDSCs in human colorectal cancer (CRC), which might allow for a new perspective on therapeutic targeting of human MDSCs with anti-CD38 monoclonal antibodies in this cancer. METHODS: Blood samples were collected from 41 CRC patients and 8 healthy donors, followed by peripheral blood mononuclear cell (PBMC) separation. Polymorphonuclear (PMN-) and monocytic (M-) MDSCs and CD38 expression levels were quantified by flow cytometry. The immunosuppressive capacity of M-MDSCs from 10 CRC patients was validated in a mixed lymphocyte reaction (MLR) assay. RESULTS: A significant expansion of CD38+ M-MDSCs and a trend of expansion of CD38+ PMN-MDSCs (accompanied by a trend of increased CD38 expression on both M- and PMN-MDSCs) were observed in PBMCs of CRC patients when compared with healthy donors. The CD38+ M-MDSCs from CRC patients were found to be immunosuppressive when compared with mature monocytes. CD38+ M- and PMN-MDSC frequencies were significantly higher in CRC patients who previously received treatment when compared with treatment-naive patients. CONCLUSIONS: This study provides a rationale for an attempt to target M-MDSCs with an anti-CD38 monoclonal antibody in metastatic CRC patients. FUNDING: NCI P01-CA14305603, the American Cancer Society, Scott and Suzi Lustgarten Family Colon Cancer Research Fund, Hansen Foundation, and Janssen Research and Development.

Role of TEFFECTOR/MEMORY Cells, TBX21 Gene Expression and T-Cell Homing Receptor on Type 1 Reaction in Borderline Lepromatous Leprosy Patients.

In spite of hyporesponsivity to Mycobacterium leprae, borderline lepromatous (BL) patients show clinical and immunological instability, and undergo frequent acute inflammatory episodes such as type 1 reaction (T1R), which may cause nerve damages. This work focused on the participation of T cell subsets from blood and skin at T1R onset. We observed a significantly increased ex vivo frequency of both effector and memory CD4+ and CD8+ T cells in T1R group. Besides, ex vivo frequency of T cell homing receptor, the Cutaneous Leukocyte-associated Antigen (CLA) was significantly increased in T cells from T1R patients. M. leprae induced a higher frequency of CD4+ TEM and CD8+ TEF cells, as well as of CD8+/TEMRA (terminally differentiated effector T cells) subset, which expressed high CD69+. The presence of IFN-γ‒producing-CD4+ TEF and naïve and effector CD8+ T lymphocytes was significant in T1R. TBX21 expression was significantly higher in T1R, while BL showed increased GATA3 and FOXP3 expression. In T1R, TBX21 expression was strongly correlated with CD8+/IFN-γ‒ T cells frequency. The number of double positive CD8+/CLA+ and CD45RA+/CLA+ cells was significantly higher in skin lesions from T1R, in comparison with non-reactional BL group. The observed increase of ex vivo T cells at T1R onset suggests intravascular activation at the beginning of reactional episodes. The antigen-specific response in T1R group confirmed the higher number of CD8+/CLA+ and CD45RA+/CLA+ cells in T1R lesions suggests possible migration of these cells activated by M. leprae components inside the vascular compartment to skin and participation in T1R physiopathology.

Plasmacytoid dendritic cells in cutaneous lesions of patients with chromoblastomycosis, lacaziosis, and paracoccidioidomycosis: a comparative analysis.

Plasmacytoid dendritic cells (pDCs) are characterized by expression of CD123 and BDCA-2 (Blood Dendritic Cell Antigen 2) (CD303) molecules, which are important in innate and adaptive immunity. Chromoblastomycosis (CBM), lacaziosis or Jorge Lobo's disease (JLD), and paracoccidioidomycosis (PCM), are noteworthy in Latin America due to the large number of reported cases. The severity of lesions is mainly determined by the host's immune status and in situ responses. The dendritic cells studied in these fungal diseases are of myeloid origin, such as Langerhans cells and dermal dendrocytes; to our knowledge, there are no data for pDCs. Forty-three biopsies from patients with CBM, 42 from those with JLD and 46 diagnosed with PCM, were evaluated by immunohistochemistry. Plasmacytoid cells immunostained with anti-CD123 and anti-CD303 were detected in 16 cases of CBM; in those stained with anti-CD123, 24 specimens were obtained from PCM. We did not detect the presence of pDCs in any specimen using either antibody in JLD. We believe that, albeit a secondary immune response in PCM and CBM, pDCs could act as a secondary source of important cytokines. The BDCA-2 (CD303) is a c-type lectin receptor involved in cell adhesion, capture, and processing of antigens. Through the expression of the c-lectin receptor, there could be an interaction with fungi, similar to other receptors of this type, namely, CD207 in PCM and CD205 and CD209 in other fungal infections. In JLD, the absence of expression of CD123 and CD303 seems to indicate that pDCs are not involved in the immune response.

Angiogenesis and lymphangiogenesis in the spectrum of leprosy and its reactional forms.

BACKGROUND: Angiogenesis and lymphangiogenesis are the processes of neovascularization that evolve from preexisting blood and lymphatic vessels. There are few studies on angiogenesis and none on lymphangiogenesis in leprosy. Thus, the role of neovascularization in the pathophysiological mechanisms of the disease was studied across the spectrum of leprosy, its reactional states and its residual lesions. METHODOLOGY/PRINCIPAL FINDINGS: Seventy-six biopsies of leprosy skin lesions and seven healthy controls were selected. Fifty-five serum samples were used for the detection of CD105 by ELISA. Histological sections were stained with antibodies against CD31 (blood and lymphatic vessels), D2-40/podoplanin (lymphatic vessels), and CD105/endoglin (neovessels). Microvessels were counted in 100 high-power fields (400x) and the number of vessels was evaluated in relation to the extension of the inflammatory infiltrate (0-3), to the bacillary index (0-6) and to the clinical forms. Angiogenesis, as marked by CD31 and CD105, was observed across the leprosy spectrum, compared with the controls. Additionally, there was a positive correlation between these markers with extension of the infiltrate (p <0.0001). For D2/40, lymphangiogenesis was observed in the tuberculoid form (p <0.0001). There was no statistical significance for values of CD105 detected in plasma by ELISA. CONCLUSIONS/SIGNIFICANCE: Angiogenesis is present across the spectrum of leprosy and in its reactional forms. The increase in the number of vessels, as detected by CD31 and CD105 staining, is related to the extension of the inflammatory infiltrate. Samples from reactional lesions have a higher number of CD31+ and CD105+ stained vessels, which indicates their involvement in the pathophysiological mechanisms of the reactional states. The regression of lesions is accompanied by the regression of neovascularization. Drugs inhibiting angiogenesis may be relevant in the treatment of leprosy, in addition to multidrugtherapy, and in the prevention of the development of reactions.

Role of CD8(+) T cells in triggering reversal reaction in HIV/leprosy patients.

It has been reported that the initiation of highly active anti-retroviral therapy (HAART) is associated with the development of reversal reaction (RR) in co-infected HIV/leprosy patients. Nevertheless, the impact of HIV and HAART on the cellular immune response to Mycobacterium leprae (ML) remains unknown. In the present study, we observed that ex vivo peripheral blood mononuclear cells (PBMCs) of both RR and RR/HIV patients presented increased percentages of activated CD4(+) T cells when compared with the healthy individuals (HC) group. The frequency of CD8(+)  CD38(+) cells increased in the PBMCs of RR/HIV patients but not in RR patients when compared with the HC group. Both RR and RR/HIV skin lesion cells presented similar percentages of activated CD4(+) cells, but the numbers of activated CD8(+) cells were higher in RR/HIV in comparison to the RR group. The frequency of interferon-γ-producing cells was high in response to ML regardless of HIV co-infection. In ML-stimulated cells, there was an increase in central memory CD4(+) T-cell frequencies in the RR and RR/HIV groups, but an increase in central memory CD8(+) T-cell frequency was only observed in the RR/HIV group. ML increased granzyme B(+) effector memory CD8(+) T-cell frequencies in the RR/HIV PBMCs, but not in the HC and RR groups. Our data suggest that the increased expression of effector memory CD8(+) T cells, together with greater perforin/granzyme B production, could be an additional mechanism leading to the advent of RR in co-infected patients. Moreoever, this increased expression may explain the severity of RR occurring in these patients.

Angiogeneis and lymphangiogenesis in the spectrum of leprosy and its reactional forms

BACKGROUND: Angiogenesis and lymphangiogenesis are the processes of neovascularization that evolve from preexisting blood and lymphatic vessels. There are few studies on angiogenesis and none on lymphangiogenesis in leprosy. Thus, the role of neovascularization in the pathophysiological mechanisms of the disease was studied across the spectrum of leprosy, its reactional states and its residual lesions. METHODOLOGY/PRINCIPAL FINDINGS: Seventy-six biopsies of leprosy skin lesions and seven healthy controls were selected. Fifty-five serum samples were used for the detection of CD105 by ELISA. Histological sections were stained with antibodies against CD31 (blood and lymphatic vessels), D2-40/podoplanin (lymphatic vessels), and CD105/endoglin (neovessels). Microvessels were counted in 100 high-power fields (400x) and the number of vessels was evaluated in relation to the extension of the inflammatory infiltrate (0-3), to the bacillary index (0-6) and to the clinical forms. Angiogenesis, as marked by CD31 and CD105, was observed across the leprosy spectrum, compared with the controls. Additionally, there was a positive correlation between these markers with extension of the infiltrate (p <0.0001). For D2/40, lymphangiogenesis was observed in the tuberculoid form (p <0.0001). There was no statistical significance for values of CD105 detected in plasma by ELISA. CONCLUSIONS/SIGNIFICANCE: Angiogenesis is present across the spectrum of leprosy and in its reactional forms. The increase in the number of vessels, as detected by CD31 and CD105 staining, is related to the extension of the inflammatory infiltrate. Samples from reactional lesions have a higher number of CD31+ and CD105+ stained vessels, which indicates their involvement in the pathophysiological mechanisms of the reactional states. The regression of lesions is accompanied by the regression of neovascularization. Drugs inhibiting angiogenesis may be relevant in the treatment of leprosy, in addition to multidrugtherapy, and in the prevention of the development of reactions.

Evaluation of the combination of BP180-NC16a enzyme-linked immunosorbent assay and BP230 enzyme-linked immunosorbent assay in the diagnosis of bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is an acquired autoimmune subepidermal blistering disease characterized by circulating IgG autoantibodies directed against BP180 and BP230 hemidesmosomal proteins. Previous studies have demonstrated that antibodies against the NC16a domain of BP180 mediate BP pathogenesis, while antibodies against BP230 enhance the inflammatory response. Recently, commercial BP180-NC16a enzyme-linked immunosorbent assay (ELISA) and BP230 ELISA kits were developed to detect anti-BP180 and anti-BP230 autoantibodies in human BP sera. AIMS: To evaluate the efficacy of BP180-NC16a ELISA and BP230 ELISA in the initial diagnosis of BP. METHODS: Sera from 62 BP patients and 62 control subjects were tested by BP180-NC16a ELISA and BP230 ELISA and compared with findings from indirect immunofluorescence (IIF) and immunoblotting (IB) to determine the sensitivity and specificity of these assays. RESULTS: The sensitivities of BP180-NC16a ELISA and BP230 ELISA were 87.1% (54/62) and 56.5% (35/62), respectively, and the specificities of both were 100% (62/62). Using both ELISAs for diagnosis increased the sensitivity to 95.2% (59/62) and was statistically comparable with IB sensitivity. CONCLUSIONS: ELISA is a convenient, effective, and reliable method for serodiagnosis of BP, and combined use of BP180-NC16a ELISA and BP230 ELISA can increase the sensitivity of this diagnostic approach.

Genetic variants of the MRC1 gene and the IFNG gene are associated with leprosy in Han Chinese from Southwest China.

Leprosy is an ancient infectious disease, with over 200,000 affected people (mainly in Asia and Africa) being registered annually. Genetic factors may confer susceptibility to this disease. In the present study, we genotyped 12 genetic variants of the MRC1 gene and the IFNG gene in 527 Han Chinese with leprosy and 583 healthy individuals from Yunnan, China, to discern potential association of these two genes with leprosy. In particular, we aimed to validate the recently reported association of MRC1 variant rs1926736 (p.G396S) and IFNG variant rs2430561 (+874 T>A) with leprosy, which were initially observed in Vietnamese and Brazilian populations, respectively. Our results failed to confirm the reported association between variants rs1926736 and rs2430561 and leprosy in Han Chinese. However, we found that variants rs692527 (P = 0.022) and rs34856358 (P = 0.022) of the MRC1 gene were associated with paucibacillary leprosy, and rs3138557 of the IFNG gene was significantly associated with multibacillary leprosy. The exact role of the MRC1 gene and the IFNG gene in leprosy awaits future study.

Association of variants in BAT1-LTA-TNF-BTNL2 genes within 6p21.3 region show graded risk to leprosy in unrelated cohorts of Indian population.

Host immune response against Mycobacterium leprae plays an important role in providing resistance to infection and disease progression. Genome-wide linkage and association studies suggest the possibility of multiple risk loci within HLA (6p21.3) region. Any systematic study of relevance within the histocompatibility complex of importance in host immune response would be pertinent because of non-replication of the known loci and unavailable information on some of the unexplored genes and regions. A systematic scan was performed of the selected region involving LTA-TNF-LTB genes within 6p21.3 with a resolution of 1SNP/127 bp; and the SNPs in flanking BAT1, NFKBIL and BTNL2-DRA genes on the basis of their tag status or their presence in promoter/exonic regions with MAF of >5%. Nine SNPs located in BAT1, LTA, TNF genes and BTNL2-DRA interval showed strong association with leprosy susceptibility in two independent sets of North Indian population which was replicated in a geographically distinct East Indian population. Conditional logistic regression showed at least one functional SNP remaining significant in each gene, suggesting an independent role of each of the disease associated SNPs. In vitro reporter assay revealed that two SNPs located at BAT1 promoter and 13 kb upstream to LTA gene affected the transcription factor binding site, hence the gene expression. We unravel the role of unexplored immunologically important genes, BAT1 and BTNL2, in addition to known LTA and TNF genes, and the haplotypes of the significantly associated SNPs therein, to understand susceptibility to the disease, leprosy and its differential severity.

Analysis of the association between BTNL2 polymorphism and tuberculosis in Chinese Han population.

BTNL2 gene, a MHC class II gene-linked butyrophilin family member, has been recently associated with the inflammatory autoimmune diseases, such as tuberculosis, sarcoidosis and leprosy. This diseases show phenotypic features of granulomatous disease. Multiple single nucleotide polymorphisms in BTNL2 have been investigated as a candidate gene for tuberculosis in a case-control association study in the South African Coloured population. But, no significant association was detected between any of the polymorphisms investigated and TB, including rs2076530 SNP that was previously found to be associated with sarcoidosis. In this study, we genotyped 6 SNPs using SNaPshot in 286 tuberculosis cases and 608 controls in Chinese. Our genetic study revealed a significant association between the rs3763313, rs9268494, rs9268492 SNPs in the BTNL2 gene and tuberculosis. And haplotypes 1-5, and 8 (C-A-G-T-G-A, C-A-G-T-G-G, C-A-T-G-C-A, C-A-T-G-C-G, and C-G-T-G-C-G, T-A-T-G-C-A) presented a significant association with susceptibility to tuberculosis. We found that BTNL2 gene was linked to tuberculosis in Chinese Han population.

Low frequency of the TIRAP S180L polymorphism in Africa, and its potential role in malaria, sepsis, and leprosy.

BACKGROUND: The Toll-like receptors (TLRs) mediate innate immunity to various pathogens. A mutation (S180L) in the TLR downstream signal transducer TIRAP has recently been reported to be common in Europeans and Africans and to roughly half the risks of heterogeneous infectious diseases including malaria, tuberculosis, bacteremia, and invasive pneumococal disease in heterozygous mutation carriers. METHODS: We assessed the TIRAP S180L variant by melting curve and RFLP analysis in 1095 delivering women from malaria-endemic Ghana, as well as in a further 1114 individuals participating in case control studies on sepsis and leprosy in Germany, Turkey and Bangladesh. RESULTS: In Ghana, the TIRAP S180L polymorphism was virtually absent. In contrast, the mutation was observed among 26.6%, 32.9% and 12% of German, Bangladesh and Turkish controls, respectively. No significant association of the heterozygous genotype with sepsis or leprosy was observed. Remarkably, homozygous TIRAP 180L tend to increase the risk of sepsis in the German study (P = 0.04). CONCLUSION: A broad protective effect of TIRAP S180L against infectious diseases per se is not discernible.

Analysis of the BTNL2 truncating splice site mutation in tuberculosis, leprosy and Crohn's disease.

The region on chromosome 6 encoding the major histocompatibility complex (MHC) is associated with a number of autoimmune and infectious diseases. Primary susceptibility to many of these has been localized to a region containing the human leukocyte antigen (HLA)-DR and -DQ genes. A recent study of sarcoidosis has provided evidence of an independent effect, associated with a truncating single nucleotide polymorphism (SNP) of a nearby gene, BTNL2. This gene may encode an immune receptor involved in costimulation. Sarcoidosis, tuberculoid leprosy, tuberculosis (TB) and Crohn's disease all have similar immunological features, including a Th1 response with granuloma formation. In addition mycobacteria have been identified or suggested to be causative pathogens in such conditions. We genotyped the truncating BTNL2 SNP in 92 TB and 72 leprosy families from Brazil and carried out family-based association studies. We could not find evidence of overtransmission of the truncating allele in TB. There was an association with susceptibility to leprosy (P=0.04), however, this is most likely due to linkage disequilibrium with HLA-DR. We also genotyped 476 UK Caucasian cases of Crohn's disease with 760 geographically matched controls and found no evidence of a disease association. We conclude that the truncating BTNL2 SNP is not important in this group of Th1 dominated granulomatous diseases.

Regulation of human T-cell homing receptor expression in cutaneous bacterial infection.

We investigated the regulation of T-cell homing receptors in infectious disease by evaluating the cutaneous lymphocyte antigen (CLA) in human leprosy. We found that CLA-positive cells were enriched in the infectious lesions associated with restricting the growth of the pathogen Mycobacterium leprae, as assessed by the clinical course of infection. Moreover, CLA expression on T cells isolated from the peripheral blood of antigen-responsive tuberculoid leprosy patients increased in the presence of M. leprae (2.4-fold median increase; range 0.8-6.1, n = 17), but not in unresponsive lepromatous leprosy patients (1.0-fold median increase; range 0.1-2.2, n = 10; P < 0.005). Mycobacterium leprae specifically up-regulated the skin homing receptor, CLA, but not alpha(4)/beta(7), the intestinal homing receptor, which decreased on T cells of patients with tuberculoid leprosy after antigen stimulation (2.2-fold median decrease; range 1.6-3.4, n = 3). Our data indicate that CLA expression is regulated during the course of leprosy infection and suggest that T-cell responsiveness to a microbial antigen directs antigen-specific T cells to the site of infection.

[Immune dysregulation mediated by hepatitis C virus infection].

Hepatitis C virus, which is non-cytopathic, establishes persistent infection in majority of patients after acute infection, causing various degrees of clinical liver disease. To escape and survive, hepatitis C virus may take ingenious strategies. Hepatitis C virus gene products interact host proteins to evade host immune responses in addition to the appearance of quasispecies. Against hepatitis C virus infection, host may avoid extensive tissue damage by inducing the activity of regulatory T cells. Insights into this mechanism of immune regulation may help to future development of novel therapies against hepatitis C virus.

The role of toll-like receptors in the pathogenesis and treatment of dermatological disease.

Toll-like receptors (TLR) are crucial players in the innate immune response to microbial invaders. These receptors are expressed on immune cells, such as monocytes, macrophages, dendritic cells, and granulocytes. Importantly, TLR are not only expressed by peripheral blood cells, but their expression has been demonstrated in airway epithelium and skin, important sites of host-pathogen interaction. Host cells expressing TLR are capable of recognizing conserved pathogen-associated molecular patterns, such as lipopolysaccharide and CpG DNA, and their activation triggers signaling pathways that result in the expression of immune response genes and cytokine production. As TLR are instrumental in both launching innate immune responses and influencing adaptive immunity, regulation of TLR expression at sites of disease such as in leprosy, acne, and psoriasis may be important in the pathophysiology of these diseases. Furthermore, since TLR are vital players in infectious and inflammatory diseases, they have been identified as potential therapeutic targets. Indeed, synthetic TLR agonists such as imiquimod have already established utility in treating viral pathogens and skin cancers. In the future, it seems possible there may also be drugs capable of blocking TLR activation and thus TLR-dependent inflammatory responses, providing new treatment options for inflammatory diseases.

TLR activation triggers the rapid differentiation of monocytes into macrophages and dendritic cells.

Leprosy enables investigation of mechanisms by which the innate immune system contributes to host defense against infection, because in one form, the disease progresses, and in the other, the infection is limited. We report that Toll-like receptor (TLR) activation of human monocytes induces rapid differentiation into two distinct subsets: DC-SIGN+ CD16+ macrophages and CD1b+ DC-SIGN- dendritic cells. DC-SIGN+ phagocytic macrophages were expanded by TLR-mediated upregulation of interleukin (IL)-15 and IL-15 receptor. CD1b+ dendritic cells were expanded by TLR-mediated upregulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor, promoted T cell activation and secreted proinflammatory cytokines. Whereas DC-SIGN+ macrophages were detected in lesions and after TLR activation in all leprosy patients, CD1b+ dendritic cells were not detected in lesions or after TLR activation of peripheral monocytes in individuals with the progressive lepromatous form, except during reversal reactions in which bacilli were cleared by T helper type 1 (TH1) responses. In tuberculoid lepromatous lesions, DC-SIGN+ cells were positive for macrophage markers, but negative for dendritic cell markers. Thus, TLR-induced differentiation of monocytes into either macrophages or dendritic cells seems to crucially influence effective host defenses in human infectious disease.

Immunostimulatory activity of major membrane protein-II from Mycobacterium leprae.

We examined the antigenicity of an immunomodulatory protein, major membrane protein (MMP)-II, from Mycobacterium leprae, since host defense against M. leprae largely depends on adaptive immunity. Both unprimed and memory T cells from healthy individuals were stimulated by autologous MMP-II-pulsed monocyte-derived dendritic cells (DCs) to produce IFN-gamma. The DC-mediated IFN-gamma production was dependent on the expression of MHC, CD86, and MMP-II antigens. Memory T cells from paucibacillary (PB) leprosy more extensively responded to MMP-II-pulsed DCs than T cells from healthy individuals, while comparable IFN-gamma was produced by unprimed T cells. Memory T cells from multibacillary leprosy, which are normally believed to be anergic, were activated similarly to those from healthy individuals by MMP-II-pulsed DCs. These results suggest that memory T cells from PB leprosy are primed with MMP-II prior to the manifestation of the disease, and MMP-II is highly antigenic in terms of activation of adaptive immunity.

[Current advances in leprosy research activities].

Due to the advent of multi-drug therapy (MDT) recommended by the WHO, for the treatment of leprosy, presently, leprosy is regarded as a "curable disease". The number of new cases in Japan is relatively very low, due to which the disease is likely to be neglected, but on scientific grounds, there is a necessity to perform in depth studies. Leprosy caused by M. leprae is still unclear on various aspects including transmission, immunology, nerve damage etc. Here we introduce the recent advances in the field of basic leprosy research.