TOXOPLASMA GONDII SERINE PROTEASE INHIBITOR-1 (rTgPI-1) SHAPING PULMONARY IMMUNE RESPONSE IN ASTHMA

JOEL KATAN PIÑEIRO; JULIETA SANTOS; VALENTINA MARTIN; ORONA, NADIA; F ASTORT; P BERGUER; FENOY I; A SOTO; A GOLDMAN

Congreso; LXXI Reunión Anual de la Sociedad Argentina de Inmunología; 2023

SAI

BACKGROUND: We previously showed that treatment with T. gondii serine protease inhibitor-1 (rTgPI-1) significantly reduced experimental asthma. BMDC differentiated in the presence of rTgPI-1 had lower CD80 and CD86 and increased PDL-1 expression which correlated with a lower capacity to activate Th2 and Th17 cells. Also, a diminished cDC2 subset in the lungs of an in vivo model of asthmatic mice treated with rTgPI-1 was detected. AIM: To further study the effects of treatment of asthmatic mice with rTgPI-1 on lung dendritic cells and the consequences over the T cell response. METHODS: BALB/c mice were ip. sensitized with OVA/Alum and aerosol challenged. Later, were intranasally treated for 3 days with rTgPI-1+OVA (OPI). Controls included naive and sensitized mice treated with OVA (OO). Twelve hours later, activation (CD80, CD86) and tolerogenic (PDL1) markers on DCs (CD11c+MHCII+), and CD4+ T cell proliferation was analyzed in the lung. Also, total lung cells were ex vivo stimulated with OVA and the supernatant was used to measure IL-4, IL-5, IL-10, IL-17, and IFN-y. Proliferation of regulatory FoxP3+CD4+ T cells, and lung resident regulatory CD4+FoxP3+CD103+ T cells was assessed by Ki67 expression 72 hours after the last treatment. RESULTS: Although no differences in PDL1 or CD86 were registered in DCs from OPI mice, a significantly lower expression of CD80 (p=0.005) was detected, which correlated with a significantly lower proliferation of total CD4+ T cells (p=0.01). Finally, culture supernatants from lungs of OPI mice showed significantly less IL-4 (p =0.02) and a trend to decreased levels of IL-5. No differences in IL-10, IL-17 and IFN-y were detected. Seventy two hours after the last treatment, there was a significantly increased percentage and proliferation of regulatory CD4+FoxP3+ T cells (p=0.02 and p=0.002 respectively) and regulatory lung resident CD4+FoxP3+CD103+ T cells (p=0.0002 and p=0.0008 respectively). CONCLUSIONS: rTgPI-1 treatment of asthmatic mice results in semi-mature lung DCs that would have lower capacity to induce Th2 activation and proliferation. The cytokine secretion profile in the lung in response to the allergen correlates with the diminished cDC2 subset previously observed. Finally, rTgPI-1 treatment also induces lung regulatory T cells expansion.