Invariant Natural Killer T Cells as Key Players in Host Resistance against Paracoccidioides brasiliensis

Author(s):Show less -

Nogueira-Neto, Joes ^[1] ; Loures, Flavio V. ^{[2, 3]} ; Schanoski, Alessandra S. ^[2] ; Andrade, David A. G. ^[1] ; Gonzatti, Michelangelo B. ^[1] ; Costa, Tania A. ^[2] ; Vivanco, Bruno C. ^[1] ; Xander, Patricia ^[4] ; Rosa, Daniela S. ^[1] ; Calich, Vera L. G. ^[2] ; Keller, Alexandre C. ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Inst Ciencia & Tecnol, Campus Sao Jose Campos, Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Ciencias Farmaceut, Campus Diadema, Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF IMMUNOLOGY RESEARCH; v. 2021, APR 16 2021.
• Web of Science Citations: 0

Abstract

Invariant Natural Killer T (iNKT) cells are key players in the immunity to several pathogens; however, their involvement in the resistance to Paracoccidioides brasiliensis infection remains unknown. Using splenocytes from CD1d (CD1d(-/-)) and iNKT-deficient (J alpha 18(-/-)) mice, we found that iNKT cells are the innate source of IFN-gamma after P. brasiliensis infection and are required to potentiate macrophage oxidative burst and control fungal growth. To determine whether iNKT cells contribute in vivo to host resistance against P. brasiliensis infection, we infected intratracheally wild-type and J alpha 18(-/-) C57BL/6 mouse strains with the virulent Pb18 isolate. iNKT cell deficiency impaired the airway acute inflammatory response, resulting in decreased airway neutrophilia and reduced IFN-gamma, KC, and nitric oxide (NO) production. The deficient innate immune response of J alpha 18(-/-) mice to Pb18 infection resulted in increased fungal burden in the lungs and spleen. Besides, the activation of iNKT cells in vivo by administration of the exogenous iNKT ligand alpha -galactosylceramide (alpha -GalCer) improved host resistance to P. brasiliensis infection. Although the mechanisms responsible for this phenomenon remain to be clarified, alpha -GalCer treatment boosted the local inflammatory response and reduced pulmonary fungal burden. In conclusion, our study is the first evidence that iNKT cells are important for the protective immunity to P. brasiliensis infection and their activation by an exogenous ligand is sufficient to improve the host resistance to this fungal infection. (AU)

• FAPESP's process: 16/02189-1 - Incorporation of glycosphingolipids into nanoparticles to immunotherapy using invariant Natural Killer T lymphocytes
• Grantee: Alexandre de Castro Keller
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/23189-0 - Modulation of Treg/Th17 responses by Aryl Hydrocarbon Receptor Ligands in the Search for an Immunotherapeutic Procedure for Pulmonary Paracoccidioidomycosis
• Grantee: Vera Lucia Garcia Calich
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/04692-1 - Th2 immune responses as a risk factor for focal segmental glomerulosclerosis
• Grantee: Alexandre de Castro Keller
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/51258-2 - Influence of the enzyme indoleamine-2,3-dioxygenase (IDO) in the differentiation and function of dendritic cells and regulatory T cells in the pulmonary paracoccidioidomycosis of resistant and susceptible mice to P. brasiliensis infection
• Grantee: Vera Lucia Garcia Calich
• Support Opportunities: Regular Research Grants