Immunohistochemical Characterisation of Innate Immune Cellular Responses in Cutaneous Leishmaniasis Caused by Leishmania donovani.

Introduction: Cutaneous leishmaniasis is a neglected tropical disease affecting humans worldwide. Leishmania donovani is the causative agent of cutaneous leishmaniasis in Sri Lanka, whereas it typically causes visceral leishmaniasis in other regional countries. Identifying pretreatment innate immune responses may offer insights into diverse disease manifestations.

Methods: We studied lesion biopsy specimens from 103 cutaneous leishmaniasis patients. Total leucocytes, keratinocyte activation, and the distribution of Langerhans cells were semi-quantified using CD45, Osteopontin, and CD1a immunohistochemistry markers. M1/M2 macrophage polarisation was assessed using CD68, HLA-DR, and CD163 immunohistochemistry markers and quantified via open-source image analysis.

Results: Langerhans cell distribution was significantly higher in early lesions (p = 0.017), whereas activated keratinocytes were more prevalent in late lesions (p = 0.004). Total leucocyte count showed no significant association with clinicopathological parameters. Sixty-six patients (64.1%) had M1-dominant macrophage profiles. Macrophage polarisation type was significantly associated with treatment outcome (p = 0.048). Among 17 patients with exclusively M2-dominant profiles, 15 (88.2%) required prolonged Sodium Stibogluconate treatment for complete healing.

Conclusions: Our findings suggest that early innate immune responses, particularly M1 macrophage polarisation, keratinocyte activation, and Langerhans cell involvement, contribute to treatment success in Sri Lankan cutaneous leishmaniasis caused by L. donovani, highlighting localised mechanisms of protective immunity.