IL-12 producing monocytes and IFN-γ and TNF-α producing T-lymphocytes are increased in placentas infected by Plasmodium falciparum

Placental Plasmodium falciparum sequestration is associated with dysregulated immune function. Placental inflammatory responses via IFN-γ and TNF-α 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-γ, TNF-α, 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-γ, TNF-α) and monocytes (IL-10, IL-12, TNF-α), was detected. In response to IE, CD4+ and CD8+ T-cells produced IFN-γ and TNF-α at similar rates in both compartments. In response to PMA/iono, the frequencies of CD4+ and CD8+ T-cells producing IFN-γ and TNF-α 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-α 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-γ in T-cells. Thus, IL-12 and IFN-α responses may synergistically allow a protective immune response in placental malaria. TNF-α production by CD4+ and CD8+ T-cells is up-regulated in P. falciparum-infected placentas, suggesting that T-cells actively participate to inflammatory responses. © 2006 Elsevier Ireland Ltd. All rights reserved.