Immune response to viscerotropic Leishmania: a comprehensive review

Area of Science:

• Immunology
• Infectious Diseases
• Parasitology

Background:

• Leishmania donovani and Leishmania infantum cause a spectrum of diseases, from asymptomatic infections to fatal visceral leishmaniasis (VL).
• Clinical diversity includes post-kala-azar dermal leishmaniasis (PKDL) and VL-associated hemophagocytic lymphohistiocytosis-mimic (VL-HLH-mimic).
• These variations stem from host immune responses and parasite immune evasion strategies.

Purpose of the Study:

• To review immunological mechanisms underlying diverse clinical manifestations of Leishmania infections.
• To focus on viscerotropic Leishmania infections in immunocompromised individuals (inborn errors of immunity, acquired immunodeficiencies).
• To clarify the relationship between VL and HLH-mimic, emphasizing diagnostic and therapeutic implications.

Main Methods:

• Narrative review of published literature from the last 5 years.
• Analysis of host-parasite immune interactions in various clinical presentations of leishmaniasis.
• Examination of immune evasion tactics employed by Leishmania parasites.

Main Results:

• Leishmania parasites use immune checkpoints to create an anti-inflammatory environment favoring survival.
• Approximately 70% of individuals mount a protective pro-inflammatory response, forming granulomas.
• Immunosuppression can lead to disease reactivation; individuals with HIV or primary immunodeficiencies have more severe infections and higher relapse rates.
• VL-HLH-mimic may represent a severe form of symptomatic VL, necessitating exclusion of VL in HLH patients.

Conclusions:

• A deep understanding of host-parasite immunology is vital for effective leishmaniasis treatment and prevention.
• Identifying immune deficiencies is crucial in patients with relapsed disease or VL-HLH-mimic.
• Distinguishing VL from HLH is critical, as treating VL can resolve immune dysregulation.