Activated cytotoxic T cells within zoonotic cutaneous leishmaniasis lesions

Abstract

Introduction Zoonotic cutaneous leishmaniasis (ZCL), due to infection by Leishmania (L). major, is characterized by polymorphic clinical manifestations which could be attributed to the host's immune response. In this study we investigated the involvement of cytotoxic cells on the outcome of the disease. Methods Expression of granzyme B (GrB), granulysine (Grly), and interferon (IFN)‐γ was evaluated within ZCL lesion specimens using the technique of real‐time quantitative polymerase chain reaction (RT‐qPCR). Immunohistochemical staining was performed using anti‐CD3, CD4, CD8, CD56, GrB, and IFN‐γ antibodies to identify the phenotype of GrB and IFN‐γ‐producing cells. Results GrB and Grly mRNA was detected within 75% and 80% of ZCL lesions, respectively. Statistical analysis demonstrated a significant correlation between levels of GrB and Grly. Interestingly, expression of these molecules correlates negatively with the lesion's age. The highest levels were measured in early lesions (E‐ZCL) (lesion age ≤1 month) comparing to late lesions (L‐ZCL) (lesion age >1 month). Otherwise, IFN‐γ mRNA was detected only within 56% and a positive correlation was found between levels of this cytokine and those of GrB. Immunohistochemical analysis showed that GrB is produced essentially by CD8+T cells whereas IFN‐γ is produced by both CD4+ and CD8+T cells. Conclusion Together our results demonstrate the presence of cytotoxic cells producing GrB and Grly within leishmaniasis cutaneous lesions.

Early reduction in PD-L1 expression predicts faster treatment response in human cutaneous leishmaniasis

“…Transcripts of inflammatory mediators including CXCL10, GZMB, CCL2 and CCR7 (receptor for CCL19), previously shown to be associated with other forms of murine (29)(30)(31) or human CL (32)(33)(34) were also found to be downregulated with initiation of treatment (Supplemental Table 3).…”

“…Surprisingly, common effector and regulatory cytokines associated with human CL 1 , including IFN-γ, IL-10, TNF, IL-7, IL-6, IL-4, TGFB1 , were not significantly different at this early time point after the start of treatment ( Extended Data Table 3 ). Transcripts of inflammatory mediators like CXCL10, GZMB, CCL2 and CCR7 (receptor for CCL19), previously shown to be associated with other forms of murine 21–23 and/or human CL 24–26 were also found to be downregulated with initiation of treatment.…”

Aspectos Imunológicos Das Leishmanioses Dermotrópicas E Viscerotrópicas

“…O parasito aproveita os estágios iniciais da infecção para se estabelecer ou se desenvolver dentro do microambiente de seus hospedeiros, em contrapartida também é a chance do hospedeiro de montar uma resposta rápida e eficaz ao parasito, eliminando-o e controlando a infecção 8,5 .…”

“…As NK, também, produzem TNF-α e citocinas anti-inflamatórias como a IL-10, além de outras quimiocinas. como por exemplo, a quimiocina CCL2 2,8,11 .…”

“…A resistência e eliminação dos parasitos são mediadas por células como os linfócitos Th1 e pela produção de citocinas inflamatórias, tais como o Interferon-Gama (IFN-γ) e o Fator de Necrose Tumoral (TNF) -α e -β, enquanto que os linfócitos Th2 e as IL-4 e IL -10 estão ligados à susceptibilidade a infecção. No entanto, é necessário um equilíbrio na resposta imune, pois a exacerbação dos linfócitos Th1 produz um aumento da destruição tecidual que caracteriza a forma clínica mucocutânea e o predomínio dos linfócitos Th2 se relaciona a progressão da leishmaniose cutânea 4,8,5,9 .…”