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<p><i>Leishmania major</i> is a protozoan parasite that cause cutaneous leishmaniasis.&#xa0;The outcome of <i>Leishmania</i> infection depends on the virulence of the parasite species,&#xa0;the host genetic background,&#xa0;and&#xa0;the host&#xa0;immune response. This study aims to investigate the functional response of macrophages infected with&#xa0;a live&#xa0;attenuated strain of <i>Leishmania major</i>. The Standard strain of <i>L. major</i> was obtained from the Pasteur Institute of Iran. The murine macrophage cell line (J774) was infected with parasites at passages 1, 4, 9 and 20. Infected macrophages were stained with Giemsa dye after 24, 48 and, 72 h post-infection. The expression of cytokine genes-including IL-12 p40, IL-12 p35, IL-1α, IFN-γ, IL-4, IL-10, TNF-α, TGF-β, IL-17 and, Autoimmune regulator (Aire) cytokines genes was evaluated in infected macrophage. As parasite virulence decreased with increasing passage number, the rate of phagocytosis increased significantly in macrophages infected with higher passages compared to passages 1, 4, and 9 (<i>P</i> ≤ 0.05). Except for IL-10, the expression profile of both pro-inflammatory and anti-inflammatory cytokine genes were similar across three passages 1, 4 and, 9. Notably, no cytokines gene expression was detected in macrophages infected with passage 20 of <i>L. major.</i> Attenuation of <i>L. major</i> resulted in reduced pathogenicity and enhanced phagocytosis by macrophages. The lack of anti-inflammatory cytokine expression, particularly IL-10, suggests that these immunomodulatory factors were not involved in parasite persistence in this model. The live attenuated <i>Leishmania</i> parasite alters macrophage activity and may serve as a promising candidate for vaccine development strategies.</p>

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Reprogramming the pathogen: immunogenic effects of live attenuated Leishmania major on macrophages cell line (J774)

  • 期刊论文

  • 发表日期：

    2026年2月16日

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  • Rezvan Dalvand,
  • Hossein Rezvan,
  • Mohammad Hossein Feiz Haddad,
  • Ehsan Mohseni,
  • Mohammad Ghasemi,
  • Sahar Hamoonnavard,
  • Habib Habibpour

摘要

Leishmania major is a protozoan parasite that cause cutaneous leishmaniasis. The outcome of Leishmania infection depends on the virulence of the parasite species, the host genetic background, and the host immune response. This study aims to investigate the functional response of macrophages infected with a live attenuated strain of Leishmania major. The Standard strain of L. major was obtained from the Pasteur Institute of Iran. The murine macrophage cell line (J774) was infected with parasites at passages 1, 4, 9 and 20. Infected macrophages were stained with Giemsa dye after 24, 48 and, 72 h post-infection. The expression of cytokine genes-including IL-12 p40, IL-12 p35, IL-1α, IFN-γ, IL-4, IL-10, TNF-α, TGF-β, IL-17 and, Autoimmune regulator (Aire) cytokines genes was evaluated in infected macrophage. As parasite virulence decreased with increasing passage number, the rate of phagocytosis increased significantly in macrophages infected with higher passages compared to passages 1, 4, and 9 (P ≤ 0.05). Except for IL-10, the expression profile of both pro-inflammatory and anti-inflammatory cytokine genes were similar across three passages 1, 4 and, 9. Notably, no cytokines gene expression was detected in macrophages infected with passage 20 of L. major. Attenuation of L. major resulted in reduced pathogenicity and enhanced phagocytosis by macrophages. The lack of anti-inflammatory cytokine expression, particularly IL-10, suggests that these immunomodulatory factors were not involved in parasite persistence in this model. The live attenuated Leishmania parasite alters macrophage activity and may serve as a promising candidate for vaccine development strategies.