Effect of Lactobacillus rhamnosus CRL1505 on the IL-17A/GM-CSF axis in the intestinal mucosa and neutrophil homeostasis of bone marrow in a model of immunosuppression by cyclophosphamide.

GRAMAJO-LÓPEZ, A.; SAAVEDRA, L.; HEBERT, E.M.; VILLENA, J.C.; ALVAREZ, S.; SALVA, S.

Mar del Plata

Congreso; Reunión Conjunta Sociedad Argentina de Investigación Clínica (SAIC), Sociedad Argentina de Inmunología (SAI) y Sociedad Argentina de Fisiología (SAFIS) 2018.; 2018

Gutmicrobiota is able to control immunity in distant tissues through regulation ofgranulopoiesis at primary immune sites as bone marrow (BM). The dietarysupplementation with probiotic Lactobacillus rhamnosus CRL1505 (Lr05)improves steady-state and emergency granulopoiesis in immunosupressed hosts.While the Lr05 viability is an important factor to achieve optimal effects, itis possible to stimulate immunity using nong-viable Lr05. The aim of this workwas to study the effect of oral administration of viable or non-viable Lr05 (Lr05Vor Lr05NV, respectively) on the IL-17A/GM-CSF axis in the intestinal mucosa andneutrophil homeostasis of bone marrow, in a model of immunosuppression bycyclophosphamide (Cy). Adult Swiss-mice were orally treated with Lr05V orLr05NV during five  consecutive days. Onday 6, lactobacilli-treated and untreated control mice received oneintraperitoneally dose of Cy (150 mg/kg). The Cy did not change the frequencyof IL17A-producing innate lymphoid cells on the small intestinal lamina propria(IL-17A+Rorgt+CD4-NKp46+). However, both Lr05V and Lr05NV are able to increase thesecells after the administration of the Cy. These results were correlated with anincrease in the levels of serum IL-17A (p<0.05), without detectingdifferences in the serum levels of GM-CSF between the different experimentalgroups. On the other hand, Cy decreased HSCs (Lin-Sca-1􀀎c-Kit􀀎) and MMP (Gr-1􀀎Ly6G􀀎Ly6C-) in BM. Lactobacillitreatments were able to significantly promote early recovery of HSCs and MMP(p<0.05). In addition, at 3 days post-Cy, Lr05V and LR05NV induced a highexpression of GM-CSF an a lower expression of CXCL12 in BM, compared with theCy control group (p<0.05). In conclusion, both Lr05V and Lr05NV are able toactivate beneficially the IL-17A/GM-CSF axis and accelerate the recovery of Cy-inducedimmunosuppression by increasing BM myeloid progenitors. Non-viable L.rhamnosus have the potential to be a good and safe resource for reducingchemotherapy-induced immunosuppressionincancer patients.