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Intramammary infections by Staphylococcus aureus: crosstalk between mammary epithelial cells and peripheral blood mononuclear cells, and how it governs immunity in the mammary gland of dairy cows

Grant number: 14/23189-4
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): June 01, 2015
Effective date (End): June 02, 2019
Field of knowledge:Agronomical Sciences - Veterinary Medicine - Animal Clinics and Surgery
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Alice Maria Melville Paiva Della Libera
Grantee:Fernando Nogueira de Souza
Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):17/07921-5 - Crosstalk between mammary epithelial cells and peripheral blood mononuclear cells in intrammary infections by Staphylococcus aureus and by distinct coagulase-negative staphylococci species and strains: development an in vitro model, BE.EP.PD


Immunological approaches have the potential for preventive and therapeutic intervention for Staphylococcus aureus mastitis and consequently for the milk chain production. Striving for a complete elimination of antimicrobial use in dairy cattle is unrealistic though a reduction is recommended and feasible. From that point of view, innovative tools enabling an increase in the natural ability of animals to resist infection could be of great value. The greatest obstacle in establishing this kind of strategies is a lack of understanding of the host immune response. Although, there are several studies that have investigated many aspects of the immune response induced by intramammary infections (IMIs) by S. aureus in dairy cows, there is a large gap in the understanding of some aspects of their pathogenesis, especially the role of mammary epithelial cells and lymphocytes. Regarding the role of mammary epithelial cells and lymphocytes is still incomplete, this study will evaluate the role of lymphocyte proliferation and mammary epithelial cells in IMIs by S. aureus. Here, we will evaluate the lymphocyte proliferation of memory B, WC1+ T ³´, T CD4+ and T CD8+ lymphocytes, and activated WC1+ T ³´, T CD4+ and T CD8+ in healthy and S. aureus infected dairy cows under a protocol of vaccination. The lymphocyte proliferation and the cytokine production by lymphocytes (IL-17A, IFN-³ and GM-CSF) were investigated using one strain of S. aureus isolated from a clinical case of mastitis and one strain of S. aureus isolated from a subclinical case of mastitis. Furthermore, the influence of mammary epithelial cells on lymphocyte proliferation will also be assessed in vitro using a co-culture assay. The adhesion and internalization into mammary epithelial cells and the induction of cytokine (IL-17C) production by mammary epithelial cells will also be evaluated under challenge with S. aureus strains isolated from different clinical statuses (clinical and subclinical infection). (AU)

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Scientific publications (16)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SANTOS, RENATA P.; SOUZA, FERNANDO N.; OLIVEIRA, ANA CLAUDIA D.; DE SOUZA FILHO, ANTONIO F.; AIZAWA, JULIANA; MORENO, LUISA Z.; CUNHA, ADRIANO F.; CORTEZ, ADRIANA; DELLA LIBERA, ALICE M. M. P.; HEINEMANN, MARCOS B.; et al. Molecular Typing and Antimicrobial Susceptibility Profile of Staphylococcus aureus Isolates Recovered from Bovine Mastitis and Nasal Samples. ANIMALS, v. 10, n. 11, . (14/23189-4, 15/10332-6)
BATISTA, CAMILA F.; SOUZA, FERNANDO N.; SANTOS, KAMILA R.; RAMOS SANCHEZ, EDUARDO M.; REIS, LUIZA CAMPOS; BERTAGNON, HELOISA G.; BLAGITZ, MAIARA G.; GOMES, RENATA C.; LAGE, ANDREY P.; HEINEMANN, MARCOS B.; et al. R-Phycoerythrin-labeled Mannheimia haemolytica for the simultaneous measurement of phagocytosis and intracellular reactive oxygen species production in bovine blood and bronchoalveolar lavage cells. VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, v. 196, p. 53-59, . (14/23189-4, 11/23936-6, 12/00749-9)
SANTOS, K. R.; SOUZA, F. N.; BLAGITZ, M. G.; BATISTA, C. F.; BERTAGNON, H. G.; GOMES, R. C.; MOLINARI, P. C. C.; DINIZ, S. A.; SILVA, M. X.; HADDAD, J. P. A.; et al. Mastite no período de transição: identificação de potenciais marcadores no sangue. Arquivo Brasileiro de Medicina Veterinária e Zootecnia, v. 70, n. 4, p. 1120-1128, . (12/08982-4, 14/23189-4, 14/06995-7)
L.C.A. PICININ; M.T. BORDIGNON-LUIZ; M.M.O.P. CERQUEIRA; I.M. TOALDO; F.N. SOUZA; M.O. LEITE; L.M. FONSECA; A.M.Q. LANA. Efeito da sazonalidade e práticas de manejo na qualidade do leite de tanque no estado de Minas Gerais - Brasil. Arquivo Brasileiro de Medicina Veterinária e Zootecnia, v. 71, n. 4, p. 1355-1363, . (14/23189-4)
SANTOS, KAMILA R.; SOUZA, FERNANDO N.; RAMOS-SANCHEZ, EDUARDO M.; BATISTA, CAMILA F.; REIS, LUIZA C.; FOTORAN, WESLEY F.; HEINEMANN, MARCOS B.; GOTO, HIRO; GIDLUND, MAGNUS; CUNHA, ADRIANO F.; et al. Staphylococcus aureus Protection-Related Type 3 Cell-Mediated Immune Response Elicited by Recombinant Proteins and GM-CSF DNA Vaccine. VACCINES, v. 9, n. 8, . (18/23572-3, 14/23189-4)
SOUZA, RODRIGO M.; SOUZA, FERNANDO N.; BATISTA, CAMILA F.; PIEPERS, SOFIE; DE VISSCHER, ANNELEEN; SANTOS, KAMILA R.; MOLINARI, PAULA C.; FERRONATTO, JOSE A.; DA CUNHA, ADRIANO FRANCA; BLAGITZ, MAIARA G.; et al. Distinct behavior of bovine-associated staphylococci species in their ability to resist phagocytosis and trigger respiratory burst activity by blood and milk polymorphonuclear leukocytes in dairy cow. JOURNAL OF DAIRY SCIENCE, v. 105, n. 2, p. 1625-1637, . (16/06297-3, 17/07921-5, 18/03685-8, 15/16871-6, 14/23189-4)
FERRONATTO, JOSE A.; FERRONATTO, THAIS C.; SCHNEIDER, MARLA; PESSOA, LINDOMAR F.; BLAGITZ, MAIARA G.; HEINEMANN, MARCOS B.; DELLA LIBERA, ALICE M. M. P.; SOUZA, FERNANDO N.. Diagnosing mastitis in early lactation: use of Somaticell (R), California mastitis test and somatic cell count. Italian Journal of Animal Science, v. 17, n. 3, p. 723-729, . (14/23189-4, 12/08982-4)
FERRONATTO, J. A.; SOUZA, F. N.; DELLA LIBERA, A. M. M. P.; DE VLIEGHER, S.; DE VISSCHER, A.; PIEPERS, S.; BLAGITZ, M. G.; HEINEMANN, M. B.. Inhibition of the growth of major mastitis-causing pathogens by non-aureus Staphylococcus isolates using the cross-streaking method. Arquivo Brasileiro de Medicina Veterinária e Zootecnia, v. 71, n. 5, p. 1745-1749, . (14/23189-4, 15/10332-6)
SOUZA, F. N.; BLAGITZ, M. G.; BATISTA, C. F.; TAKANO, V, P.; GARGANO, R. G.; DINIZ, S. A.; SILVA, M. X.; FERRONATTO, J. A.; SANTOS, K. R.; HEINEMANN, M. B.; et al. Immune response in nonspecific mastitis: What can it tell us?. JOURNAL OF DAIRY SCIENCE, v. 103, n. 6, p. 5376-5386, . (14/23189-4, 09/50672-0)
TAKANO, PAULO VITOR; DE CEZARO SCAPINI, VINICIUS ANDRE; VALENTINI, TALITA; GIRARDINI, LILIAN KOLLING; DE SOUZA, FERNANDO NOGUEIRA; MELVILLE PAIVA DELLA LIBERA, ALICE MARIA; HEINEMANN, MARCOS BRYAN; CHANDE, CARLA GASPAROTTO; CORTEZ, ADRIANA; COLLET, SILVANA GIACOMINI; et al. Milk cellularity and intramammary infections in primiparous and multiparous Lacaune ewes during early lactation. Small Ruminant Research, v. 167, p. 117-122, . (14/23189-4)
BEUCKELAERE, LISA; DE VISSCHER, ANNELEEN; SOUZA, FERNANDO NOGUEIRA; MEYER, EVELYNE; HAESEBROUCK, FREDDY; PIEPERS, SOFIE; DE VLIEGHER, SARNE. Colonization and local host response following intramammary Staphylococcus chromogenes challenge in dry cows. VETERINARY RESEARCH, v. 52, n. 1, . (17/07921-5, 14/23189-4)
MARQUES, MICHELE FLAVIA SOUSA; DE MOURA, GUILHERME SANTANA; DE SOUZA, FERNANDO NOGUEIRA; GARGANO, RONALDO GOMES; SANTOS, KAMILA REIS; FERRONATTO, JOSE AUGUSTO; DELLA LIBERA, ALICE MARIA MELVILLE PAIVA; MOTA, RINALDO APARECIDO. Blood polymorphonuclear leukocyte responses against Staphylococcus aureus in primiparous and pluriparous Lacaune and Santa Ine circumflex accent s ewes. Small Ruminant Research, v. 201, . (14/23189-4, 18/03685-8)
F.N. SOUZA; T. LEIVA; R.O. RODRIGUES; J.R. GANDIN JÚNIOR; E. DRAGO; R.C. GOMES; K.R. SANTOS; M.G. BLAGITZ; A.M.M.P. DELLA LIBERA; J.L.M. VASCONCELOS; et al. [Proliferação de linfócitos em vacas leiteiras suplementadas com um aditivo alimentar imunomodulador e vacinadas com vacina polivalente]. Arquivo Brasileiro de Medicina Veterinária e Zootecnia, v. 72, n. 6, p. 2397-2401, . (14/23189-4)
CUNHA, A. F.; ANDRADE, H. M.; SOUZA, F. N.; FIALHO JUNIOR, L. C.; ROSA, D. L. S. O.; RAMOS SANCHEZ, E. M.; GIDLUND, M.; GOTO, H.; BRITO, M. A. V. P.; GUIMARAES, A. S.; et al. Comparison of antibody repertories against Staphylococcus aureus in healthy and infected dairy cows with a distinct mastitis history and vaccinated with a polyvalent mastitis vaccine. JOURNAL OF DAIRY SCIENCE, v. 103, n. 5, p. 4588-4605, . (14/23189-4)
GUILHERME S. MOURA; RINALDO A. MOTA; MICHELE F.S. MARQUES; ATZEL C.A. ABAD; LUCIANA B.B.C. COSTA; FERNANDO N. SOUZA; VALDIR M. ALMEIDA; GIVALDO B. SILVA FILHO; HISADORA A.S.C. BOM; FRANCINE KLAUMANN; et al. Mastite gangrenosa em ovinos causada por Staphylococcus haemolyticus multirresistente. Pesquisa Veterinária Brasileira, v. 40, n. 12, p. 947-954, . (14/23189-4)

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