Notch Signaling is Required for Dendritic Cell Maturation and T Cell Expansion in Paracoccidioidomycosis

Area of Science:

• Immunology
• Cell Biology
• Mycology

Background:

• The Notch signaling pathway regulates critical cellular functions, including immune cell development and response.
• Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, particularly in fungal infections like paracoccidioidomycosis.
• Understanding DC function in paracoccidioidomycosis pathogenesis is crucial for developing effective therapeutic strategies.

Purpose of the Study:

• To investigate the influence of Notch signaling on DC maturation and function in the context of experimental paracoccidioidomycosis.
• To elucidate the role of Notch-activated DCs in T cell-mediated immune responses during infection with *Paralucens brasiliensis*.

Main Methods:

• Bone marrow-derived DCs were infected with *Paralucens brasiliensis* strain 18.
• Notch signaling was activated, and its effect on DC maturation markers (CD80, CD86, CCR7, CD40) and cytokine release (IL-6, TNF-α) was assessed.
• The γ-secretase inhibitor DAPT was used to block Notch signaling and evaluate its impact on DC-induced T cell proliferation.

Main Results:

• Activation of Notch signaling enhanced the maturation of *Paralucens brasiliensis*-infected DCs, evidenced by increased expression of CD80, CD86, CCR7, and CD40.
• Activated DCs released higher levels of pro-inflammatory cytokines, including IL-6 and TNF-α.
• Inhibition of Notch signaling with DAPT significantly impaired the proliferation of T cells stimulated by infected DCs.

Conclusions:

• Notch signaling effectively promotes DC maturation in response to *Paralucens brasiliensis* infection.
• The pathway is essential for DC-mediated activation of T cell responses during paracoccidioidomycosis.
• Targeting Notch signaling could be a potential therapeutic approach for managing this fungal disease.