To assess the interaction of Pneumocystis carinii with dendritic cells (DCs), and the consequences of the response of the host immune system to P. carinii antigens when DC are pulsed with P. carinii, murine DC were pulsed with P. carinii, and the resultant P. carinii host responses assessed in vitro and in vivo. P. carinii interacted with murine bone marrow-derived DC in vitro in part via mannose receptors. DC pulsed with P. carinii did not demonstrate increased expression of the cell surface markers MHC II, CD40, CD54, CD80 (B7.1), and CD86 (B7.2). The release of interleukin (IL)-4 was increased, but there was no increase in the release of interleukin (IL)-12p40, IL-10, tumor necrosis factor-alpha, IL-6, and nitrite compared with naive DC. In vivo administration of DC pulsed with P. carinii induced a P. carinii-specific response, generating CD4+ cells that proliferated and released IL-4, but not interferon-gamma, in response to P. carinii-pulsed DC in vitro. In vivo administration of DC pulsed with P. carinii also induced P. carinii-specific immunoglobulin (Ig)G1, IgG2a, and IgG2b, but not IgG3, antibodies in serum, and lung lavage fluid. Finally, CD4+ depleted mice immunized with DC pulsed with P. carinii demonstrated suppression of lung growth of P. carinii after intratracheal challenge with P. carinii at 3 and 16 weeks after immunization. These observations provide insight into DC-P. carinii interactions, and support the concept that a vaccine that includes DC pulsed with P. carinii can mount a humoral and T helper 2-type cellular response to P. carinii sufficient to suppress the growth of P. carinii in the lung.