PLoS Negl Trop Dis. 2013 Jul 25;7(7):e2328.

Immunological Profile of HTLV-1-Infected Patients Associated with Infectious or Autoimmune Dermatological Disorders

Coelho-dos-Reis JG, Passos L, Duarte MC, Araújo MG, Campi-Azevedo AC, Teixeira-Carvalho A, Peruhype-Magalhães V, Trindade BC, Dos Santos Dias R, Martins ML, Carneiro-Proietti AB, Guedes AC, Gonçalves DU, Martins-Filho OA.

Laboratório de Biomarcadores de Diagnóstico e Monitoração, Instituto René Rachou, FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.

 

ABSTRACT:

In the present study, the frequency, the activation and the cytokine and chemokine profile of HTLV-1 carriers with or without dermatological lesions were thoroughly described and compared. The results indicated that HTLV-1-infected patients with dermatological lesions have distinct frequency and activation status when compared to asymptomatic carriers. Alterations in the CD4(+)HLA-DR(+), CD8(+) T cell, macrophage-like and NKT subsets as well as in the serum chemokines CCL5, CXCL8, CXCL9 and CXCL10 were observed in the HTLV-1-infected group with skin lesions. Additionally, HTLV-1 carriers with dermatological skin lesions showed more frequently high proviral load as compared to asymptomatic carriers. The elevated proviral load in HTLV-1 patients with infectious skin lesions correlated significantly with TNF-α/IL-10 ratio, while the same significant correlation was found for the IL-12/IL-10 ratio and the high proviral load in HTLV-1-infected patients with autoimmune skin lesions. All in all, these results suggest a distinct and unique immunological profile in the peripheral blood of HTLV-1-infected patients with skin disorders, and the different nature of skin lesion observed in these patients may be an outcome of a distinct unbalance of the systemic inflammatory response upon HTLV-1 infection.

PMID: 23936564

 

SUPPLEMENT:

Human T-lymphotropic virus 1 (HTLV-1) was the first retrovirus discovered with human clinical importance [1]. While the majority of patients infected with HTLV-1 may remain asymptomatic (95%), some patients (0.2–5%) can develop severe clinical symptoms [2,3]. Among them, the dermatological disorders associated with HTLV-1 have been poorly investigated, which poses a challenge on the management – prognosis and treatment – of patients with such disorders. In the present study, the frequency, the activation and the cytokine and chemokine profile of HTLV-1 carriers with or without dermatological lesions were thoroughly described and compared. The results revealed a unique cytokine and chemokine profile of HTLV-1carriers with dermatological lesions. HTLV-1-infected patients with dermatological lesions have distinct frequency and activation status when compared to asymptomatic carriers. Alterations in the CD4+HLA-DR+, CD8+ T cell, macrophage-like and NKT subsets were observed in the HTLV-1-infected group with skin lesions. The monocytic populations seem to be altered in HTLV-1 patients with skin lesions. The macrophage-like monocytes (CD14+CD16 +/CD14+) were increased in the HTLV-1 group with skin lesions while the proinflammatory monocytes (CD14+CD16+HLA-DR++/CD14+CD16+) were decreased in both HTLV-1-infected groups with and without skin lesions.

These results are in agreement with previous results that showed downregulation of CD14 exerted by HTLV-1 infection and impairment of differentiation of monocytes into macrophages or dendritic cells from HTLV-1-infected patients. [4,5]. This unbalance of the monocytic subsets in the peripheral blood could ultimately affect migration and homing of monocyte-derived subsets, such as dendritic cells in the tissues, which may breach the skin defenses and allowing for lesion formation in HTLV-1-infected patients [5]. Serum chemokines CCL5, CXCL8, CXCL9 and CXCL10 were also altered in the presence of viral infection. In vitro evidence of HTLV-1 induction of chemokine secretion were reported showing that patients as well as cell lines infected with HTLV-1 express chemokines such as CCL2, CCL3, CCL4, CCL5, CXCL8, CXCL10 and CCL22 [6-10].

Additionally, HTLV-1 carriers with dermatological skin lesions showed more frequently high proviral load as compared to asymptomatic carriers. The elevated proviral load in HTLV-1 patients with infectious skin lesions correlated significantly with TNF-a/IL-10 ratio, while the same significant correlation was found for the IL-12/IL-10 ratio and the high proviral load in HTLV-1-infected patients with autoimmune skin lesions. While the HTLV-1-infected group with infectious dermatological lesions presented increased frequency of CD8+ T cells, the HTLV-1-infected group with autoimmune skin lesions showed increased levels of CD4+HLA-DR+T cells. These different T cell populations could provide a microenvironment that modulates the production of TNF-a and especially IL-12 from macrophage-like monocytes, which are increased in patients with skin lesions (Figure 1).

All in all, these results suggest a distinct and unique immunological profile in the peripheral blood of HTLV-1-infected patients with skin disorders, and the different nature of skin lesion observed in these patients may be an outcome of a distinct unbalance of the systemic inflammatory response upon HTLV-1 infection.

Figure-1Figure 1. Snapshot of the systemic immunity against HTLV-1 in carriers with skin lesions of infectious or autoimmune nature. The schematic representation illustrates the cytokines, chemokines and cell populations altered in the peripheral blood of patients chronically infected by HTLV-1 with infectious or autoimmune skin lesions. These immunological features give insight to the understanding of how the immune systemic biomarkers may be involved in the generation of protective and pathogenic responses and their potential association with proviral load and skin lesion.

 

References:

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