Role of Systemic Immune Response in the Development of Cutaneous Leishmaniasis

Tind Teleria^*
*Correspondence: Tind Teleria, Department of Immunology, Kindai University, Wakayama, Japan, Email:

Keywords

Cutaneous leishmaniasis • Systemic immune response • Innate immunity

Introduction

Cutaneous Leishmaniasis (CL) represents a significant public health concern in many tropical and subtropical regions, caused by various species of the protozoan parasite Leishmania transmitted by the bite of infected sand flies. The disease presents with a spectrum of clinical manifestations, from localized cutaneous lesions to more severe mucocutaneous or disseminated forms. The pathogenesis of CL is intricately linked to the systemic immune response, involving both innate and adaptive immune mechanisms. Upon inoculation by an infected sand fly, Leishmania parasites encounter host immune cells at the site of entry, triggering a cascade of innate immune responses.They can evade phagocytosis, inhibit macrophage activation and modulate cytokine production to create a permissive environment for their survival and proliferation. The establishment of Leishmania infection in the skin is characterized by the formation of granulomatous lesions, where infected macrophages, T cells and other immune cells interact in a complex microenvironment [1].

Literature Review

Macrophages, as the primary target cells for Leishmania, recognize parasite-derived molecules through Pattern Recognition Receptors (PRRs) such as Toll-Like Receptors (TLRs) and initiate phagocytosis. However, Leishmania parasites have evolved sophisticated strategies to subvert macrophage microbicidal mechanisms, including inhibition of phagolysosome fusion and modulation of host cell signaling pathways. Cutaneous Leishmaniasis (CL) is a widespread parasitic infection transmitted through the bite of infected sandflies. The disease manifests in a spectrum of clinical presentations, from self-healing localized lesions to disfiguring mucocutaneous forms. The host immune response to Leishmania infection determines the outcome of disease, ranging from effective parasite control to chronic pathology. Understanding the intricate interactions between the in situ and systemic immune responses is crucial for devising targeted interventions against CL. The skin serves as the primary battleground between Leishmania parasites and the host immune system [2,3].

In response to parasite invasion, infected macrophages release proinflammatory cytokines such as Tumor Necrosis Factor-Alpha (TNF-α), Interleukin-1 (IL-1) and Interleukin-12 (IL-12), which promote recruitment and activation of innate immune cells, including neutrophils and dendritic cells. Neutrophils contribute to the early control of parasite replication through the release of antimicrobial peptides and reactive oxygen species. However, persistent neutrophil infiltration may exacerbate tissue damage and inflammation, leading to lesion development. The adaptive immune response plays a crucial role in controlling Leishmania infection and modulating disease outcome. CD4+ T Helper (Th) cells orchestrate the adaptive immune response by differentiating into distinct subsets, including Th1, Th2 and Regulatory T cells (Tregs), characterized by their cytokine profiles and effector functions. Th1 cells, producing Interferon-Gamma (IFN-γ) and IL-2 are critical for macrophage activation and parasite killing. In contrast, Th2 cells, secreting IL-4, IL-5 and IL-13, promote alternative macrophage activation and tissue repair but may also facilitate parasite persistence [4].

The balance between Th1 and Th2 responses is crucial in determining disease outcome in CL. While an effective Th1 response is associated with parasite clearance and lesion resolution, a dominant Th2 response correlates with disease progression and chronicity. Furthermore, dysregulation of regulatory T cell function may impair immune tolerance and exacerbate tissue inflammation in CL. Leishmania parasites employ various immune evasion mechanisms to evade host immune responses and establish chronic infection. These include modulation of host cell signaling pathways, alteration of surface molecules to evade immune recognition and induction of regulatory immune responses. Additionally, Leishmania parasites can survive within host cells by exploiting host lipid metabolism and subverting apoptotic pathways [5].

Discussion

Leishmania promastigotes encounter resident immune cells, including macrophages, dendritic cells and neutrophils. The initial inflammatory response involves the recruitment of neutrophils to the site of infection, followed by the activation of macrophages and dendritic cells. These phagocytic cells attempt to engulf and eliminate the parasites through oxidative mechanisms and cytokine signaling. However, Leishmania parasites have evolved sophisticated strategies to subvert host immune defenses. Additionally, the identification of parasite-derived antigens and immunomodulatory molecules may inform the development of novel vaccine candidates capable of inducing protective immunity against CL. The heterogeneity of immune responses observed in CL underscores the importance of host factors, parasite species and environmental factors in shaping disease outcome. Genetic susceptibility factors influencing host immune responses and parasite virulence factors impacting parasite evasion strategies contribute to the complex interplay between host and pathogen. Furthermore, the development of drug resistance in Leishmania parasites poses a significant challenge to CL treatment and control efforts. Novel therapeutic agents targeting essential parasite pathways or host factors involved in immune evasion may overcome drug resistance and improve treatment outcomes in CL patients [6].

Conclusion

Moreover, as our understanding of the systemic immune response in Cutaneous Leishmaniasis (CL) continues to evolve, it is essential to address the complexity of host-parasite interactions and the variability in clinical presentations across different Leishmania species and geographic regions. Collaborative efforts between researchers, clinicians and public health officials are imperative to advance the development and implementation of innovative approaches for CL management and control. Future research efforts should focus on elucidating the molecular mechanisms underlying immune dysregulation in CL and translating these findings into novel interventions for disease prevention and control.

Acknowledgement

None.

Conflict of Interest

There are no conflicts of interest by author.

References

1. Handler, Marc Z., Parimal A. Patel, Rajendra Kapila and Yasin Al-Qubati, et al. "Cutaneous and mucocutaneous leishmaniasis: Differential diagnosis, diagnosis, histopathology and management." J Am Acad Dermatol 73 (2015): 911-926.

   Google Scholar, Crossref, Indexed at

2. Saidi, Nasreddine, Romain Blaizot, Ghislaine Prévot and Karim Aoun, et al. "Clinical and immunological spectra of human cutaneous leishmaniasis in North Africa and French Guiana." Front Immunol 14 (2023): 1134020.

   Google Scholar, Crossref, Indexed at

3. Bittencourt, Achilea L., Aldina Barral and Jackson ML Costa. "Tegumentary leishmaniasis in childhood." Pediatr Dermatol 13 (1996): 455-463.

   Google Scholar, Crossref, Indexed at

4. Boggild, Andrea K., Ana P. Ramos, Diego Espinosa and Braulio M. Valencia, et al. "Clinical and demographic stratification of test performance: A pooled analysis of five laboratory diagnostic methods for American cutaneous leishmaniasis." Am J Trop Med Hyg 83 (2010): 345.

   Google Scholar, Crossref, Indexed at

5. Bacellar, Olívia, Hélio Lessa, Albert Schriefer and Paulo Machado, et al. "Up-regulation of Th1-type responses in mucosal leishmaniasis patients." Infect Immun 70 (2002): 6734-6740.

   Google Scholar, Crossref, Indexed at

6. Cunha, C. F., R. Ferraz, M. I. F. Pimentel and M. R. Lyra, et al. "Cytotoxic cell involvement in human cutaneous leishmaniasis: Assessments in active disease, under therapy and after clinical cure." Parasite Immunol 38 (2016): 244-254.

   Google Scholar, Crossref, Indexed at