Regulatory T Cells in the Pathogenesis and Healing of Chronic Human Dermal Leishmaniasis Caused by Leishmania (Viannia) Species

The immune inflammatory response is a double edged sword. During infectious diseases, regulatory T cells can prevent eradication of the pathogen but can also limit inflammation and tissue damage. We investigated the role of regulatory T cells in chronic dermal leishmaniasis caused by species of the parasite Leishmania that are endemic in South and Central America. We found that although individuals with chronic lesions have increased regulatory T cells in their blood and at skin sites where immune responses to Leishmania were taking place compared to infected individuals who do not develop disease, their capacity to control the inflammatory response to Leishmania was inferior. However, healing of chronic lesions at the end of treatment was accompanied by an increase in the number and capacity of regulatory T cells to inhibit the function of effector T cells that mediate the inflammatory response. Different subsets of regulatory T cells, defined by the expression of molecular markers, were identified during chronic disease and healing, supporting the participation of distinct regulatory T cells in the development of disease and the control of inflammation during the healing response. Immunotherapeutic strategies may allow these regulatory T cell subsets to be mobilized or mitigated to achieve healing

Clinical features, fungal load, coinfections, histological skin changes, and itraconazole treatment response of cats with sporotrichosis caused by Sporothrix brasiliensis

SOUZA, Elaine Waite de et al. Clinical features, fungal load, coinfections, histological skin changes, and itraconazole treatment response of cats with sporotrichosis caused by Sporothrix brasiliensis. Scientific Reports, v. 8, p. 1-10, 2018.Submitted by Rodrigo Menezes ([email protected]) on 2018-07-15T23:56:46Z No. of bitstreams: 1 Souza_et_al-2018-Scientific_Reports.pdf: 1890404 bytes, checksum: d0fc4182b13d4a922bcba16273624d7e (MD5)Approved for entry into archive by Raquel Dinelis ([email protected]) on 2018-07-30T18:13:40Z (GMT) No. of bitstreams: 1 Souza_et_al-2018-Scientific_Reports.pdf: 1890404 bytes, checksum: d0fc4182b13d4a922bcba16273624d7e (MD5)Made available in DSpace on 2018-07-30T18:13:40Z (GMT). No. of bitstreams: 1 Souza_et_al-2018-Scientific_Reports.pdf: 1890404 bytes, checksum: d0fc4182b13d4a922bcba16273624d7e (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.School of Veterinary Medicine. Louisiana State University, Baton Rouge. Los Angeles, USA.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Zoonotic sporotrichosis caused by the fungus Sporothrix brasiliensis is usually severe in cats. This study investigated the associations between clinical features, fungal load, coinfections, histological skin changes, and response to itraconazole in cats with sporotrichosis caused by S. brasiliensis. Fifty-two cats with skin lesions and a definitive diagnosis of sporotrichosis were treated with itraconazole for a maximum period of 36 weeks. The animals were submitted to clinical examination and two subsequent collections of samples from the same skin lesion for fungal diagnosis and histopathology, as well as serology for feline immunodeficiency (FIV) and leukaemia (FeLV) viruses. Thirty-seven (71%) cats were clinically cured. Nasal mucosa lesions and respiratory signs were associated with treatment failure. Cats coinfected with FIV/FeLV (n = 12) had a lower neutrophil count in the lesion. A high fungal load in skin lesions was linked to young age and treatment failure, as well as to a longer time of wound healing, poorly formed granulomas and fewer neutrophils, macrophages and lymphocytes in these lesions. These results indicate that itraconazole is effective, but nasal mucosal involvement, respiratory signs and high fungal loads in skin lesions are predictors of treatment failure that will assist in the development of better treatment protocols for cats