Immunobiotic Lactobacillus strains ameliorate myelopoietic alterations and improve resistance against Streptococcus pneumoniae in cyclophosphamide-immunosuppressed mice

ANDRES GRAMAJO LOPEZ; YANINA KOLLING; JULIO VILLENA; HORTENSIA ZELAYA; SUSANA ALVAREZ; SUSANA SALVA

Buenos Aires

Congreso; The First International Joint Meeting between the Latin American Society for Immunodeficiencies (LASID), the Argentinean Society for Immunology (SAI), and the French Society for Immunology (SFI); 2015

Sociedad Argentina de Inmunología

IMMUNOBIOTIC Lactobacillus STRAINS AMELIORATE MYELOPOIETIC ALTERATIONS AND IMPROVE RESISTANCE AGAINST Streptococcus pneumoniae IN CYCLOPHOSPHAMIDE-IMMUNOSUPPRESSED MICEAndrés Gramajo-López1,2, Yanina Kolling1,3, Julio Villena1,3, Susana Alvarez1,2,3, Susana Salva1,3*1 Immunobiotics Research Group, 2 Institute of Applied Biochemistry, Tucuman University. Tucuman, Argentina.3 CERELA-CONICET. Tucuman, Argentina.* Corresponding author. Mailing address for Susana Salva: Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET). Tucuman, Argentina. Phone: +54-381-4310465. Fax: +54-381-4005600. E-mail address: ssalva@cerela.org.ar Background: Cyclophosphamide (Cy), a widely used alkylating anti-cancer drug, has several serious side effects including myelosuppression, and immunosuppression. The aim of this work was to evaluate whether immunobiotic Lactobacillus strains were able reduce Cy-induced hematopoietic alterations and improve emergency granulopoiesis induced by Streptococcus pneumoniae (Sp) infection.Methods: Adult Swiss-mice were orally treated with viable or non-viable Lactobacillus rhamnosus CRL1505 (Lr05V or Lr05NV, respectively) or Lactobacillus plantarum CRL1506 (Lp06V or Lp06NV) during five consecutive days. On day 6, lactobacilli-treated and untreated control mice received one dose of Cy (150 mg/kg) intraperitoneally. On day 3 post-Cy administration, mice were nasally challenged with Sp (107, 109 or 1011 UFC/mice). Innate and myelopoietic responses were evaluated before and after the pneumococcal challenge.Results: Cy impaired myelopoiesis and increased susceptibility to pneumococcal infection. Lactobacilli treatments were able to significantly reverse those effects. However, Lr05V and Lr05NV treatments were more effective than Lp06V and Lp06NV to increase bone marrow immature myeloid progenitors (CD34+ and CD34+Gr-1+ cells), which allowed an early recovery of myeloid cells after Cy administration. In addition, both Lr05V and Lr05NV induced a recovery of blood neutrophils, improved bone marrow emergency granulopoiesis and increased the resistance against Sp. Conclusions: Both viable and non-viable L. rhamnosus CRL1505 are able to accelerate the recovery of Cy-induced immunosuppression by increasing bone marrow myeloid progenitors. This effect improves protection against respiratory pathogens in mice undergoing chemotherapy. Non-viable L. rhamnosus have the potential to be a good and safe resource for reducing chemotherapy-induced immunosuppression in cancer patients.Key words: Myelopoiesis, Lactobacilli, immunobiotic, cyclophosphamide, Streptococcus pneumoniae.