Systemic Immune Response in the Pathogenesis of Cutaneous Leishmaniasis

Tindea Mechteleria^*
*Correspondence: Tindea Mechteleria, Department of Immunology, Kindai University, Wakayama 649-6493, Japan, Email:

Keywords

Cutaneous leishmaniasis • Systemic immune response • Innate immunity • Cytokines

Introduction

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. Upon inoculation, Leishmania promastigotes encounter resident immune cells, including macrophages, dendritic cells and neutrophils [1]. 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. 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 [2].

Literature Review

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. 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 [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

Understanding the systemic immune response in CL is essential for the development of effective therapeutic interventions and vaccines. Targeting key immune checkpoints and dysregulated pathways may enhance host resistance to infection and promote lesion resolution. Strategies aimed at boosting Th1 responses or inhibiting Th2-driven immunopathology show promise as potential immunotherapeutic approaches for CL. 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 [5,6].

Conclusion

The systemic immune response plays a central role in the pathogenesis of cutaneous leishmaniasis, orchestrating a complex interplay between host defense mechanisms and parasite evasion strategies. Insights gained from understanding the dynamic interactions between innate and adaptive immune components, cytokine networks and immune evasion mechanisms not only deepen our understanding of parasite-host interactions but also offer potential avenues for the development of immunotherapeutic strategies and vaccines. 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. Moreover, as our understanding of the systemic immune response in Cutaneous Leishmaniasis (CL) continues to evolve, it is essential to address the complexity of hostparasite 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.

Acknowledgment

None.

Conflict of Interest

There are no conflicts of interest by author.

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