Visceral Leishmaniasis in Immunocompetent Hosts in Brescia: A Case Series and Analysis of Cytokine Cascade

Author:

Mulè Alice1,Crosato Verena1,Kuhns Douglas Byron2,Lorenzi Luisa3ORCID,Chirico Claudia4,Maifredi Giovanni5ORCID,Notarangelo Luigi D.6,Castelli Francesco1,Tomasoni Lina R.7

Affiliation:

1. Unit of Infectious and Tropical Diseases, Department of Clinical and Experimental Sciences, University of Brescia and ASST Spedali Civili di Brescia, 25123 Brescia, Italy

2. Neutrophil Monitoring Laboratory, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD 20701, USA

3. Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy

4. Department of Hygiene and Health Prevention, Health Protection Agency of Brescia (ATS Brescia), 25124 Brescia, Italy

5. Epidemiology Unit, Health Protection Agency of Brescia (ATS Brescia), 25124 Brescia, Italy

6. Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD 20852, USA

7. Unit of Infectious and Tropical Diseases, ASST Spedali Civili di Brescia, 25123 Brescia, Italy

Abstract

Visceral leishmaniasis (VL) is a parasitic zoonosis caused by Leishmania spp. that usually manifests itself in immunocompromised subjects. It is a rare and neglected disease, and it is not endemic in the province of Brescia (Italy). Three cases of human VL occurred in Brescia from October to December 2021 in immunocompetent patients. We evaluated the patients looking for signs of underlying immunodeficiencies and conducted further epidemiological evaluations in the province of Brescia without success. An analysis of the sera levels of the main cytokines involved in the immune response to VL was performed. All patients presented a significant augmentation of CXCL-10, CCL-4, and IL-6. The patients tested during the acute phase showed an elevation of IL-1α, IL-5, IL-10, and IL-12, while in the recovery phase, higher levels of TNF-α and IL-7 were detected. Altogether, a predominant activation of the T-helper-2 pathway emerged during the acute phase of the parasite infection, while the cytokines associated with the T-helper-1 pathway were less represented. This imbalanced immune response to the parasite infection might play a crucial role in the development of VL in immunocompetent patients.

Publisher

MDPI AG

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