title: IL-12 producing monocytes and IFN-gamma and TNF-alpha producing T-lymphocytes are increased in placentas infected by Plasmodium falciparum.
abstract: Placental Plasmodium falciparum sequestration is associated with dysregulated immune function. Placental inflammatory responses via IFN-gamma and TNF-alpha are implicated in functional damage. However, they are needed during placental infection to control asexual stage parasites. To test the hypothesis that placental immunomodulation associated with malaria disturbs cytokine secretion differently in monocytes and lymphocytes, we have determined the proportion of monocytes and/or lymphocytes secreting IFN-gamma, TNF-alpha, IL-10 and IL-12. Intervillous and peripheral blood monocyte (CD14+) and lymphocyte (CD3/CD4+; CD3/CD8+) cytokine production was compared between 17 P. falciparum-infected and 12 non-infected Senegalese women. After culture with phorbolmyristate acetate/ionomycin (PMA/iono), lipopolysaccharide (LPS) or P. falciparum-infected erythrocytes (IE), the intracellular expression of cytokines in lymphocytes (IFN-gamma, TNF-alpha) and monocytes (IL-10, IL-12, TNF-alpha), was detected. In response to IE, CD4+ and CD8+ T-cells produced IFN-gamma and TNF-alpha at similar rates in both compartments. In response to PMA/iono, the frequencies of CD4+ and CD8+ T-cells producing IFN-gamma and TNF-alpha were similar in both compartments, but increased in P. falciparum-infected placentas. In response to LPS or IE, IL-12 secreting monocytes were increased in infected women, while the frequency of TNF-alpha secreting monocytes was decreased compared to that in non-infected placenta. The monocyte IL-12 response is not impaired in infected women. IL-12 is an important factor for inducing IFN-gamma in T-cells. Thus, IL-12 and IFN-alpha responses may synergistically allow a protective immune response in placental malaria. TNF-alpha production by CD4+ and CD8+ T-cells is up-regulated in P. falciparum-infected placentas, suggesting that T-cells actively participate to inflammatory responses.
authors.affiliation: UR 010, Mother and Child Health in the Tropics, Institut de Recherche pour le Développement (IRD), BP 1386, Dakar, Senegal.
authors.forename: Ibrahima
authors.initials: I
authors.lastname: Diouf
authors.forename: Nadine
authors.initials: N
authors.lastname: Fievet
authors.forename: Souleymane
authors.initials: S
authors.lastname: Doucouré
authors.forename: Mamadou
authors.initials: M
authors.lastname: Ngom
authors.forename: Muriel
authors.initials: M
authors.lastname: Andrieu
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Mathieu
authors.forename: Alioune
authors.initials: A
authors.lastname: Gaye
authors.forename: Omar Thiom
authors.initials: OT
authors.lastname: Thiaw
authors.forename: Philippe
authors.initials: P
authors.lastname: Deloron
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology; D009000:Monocytes / Q000276:immunology*; D010920:Placenta / Q000276:immunology* / Q000469:parasitology; D010922:Placenta Diseases / Q000276:immunology* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000276:immunology* / Q000469:parasitology; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma