title: Host immune response is severely compromised during lethal Plasmodium vinckei infection.
abstract: Cytokines and immune effector cells play an important role in determining the outcome of infection with various intracellular pathogens, including protozoan parasites. However, their role during lethal and nonlethal malaria needs further validation. In the present study, we examined the role of cytokines and various immune effector cells during lethal and nonlethal malaria caused by Plasmodium vinckei in AKR mice. We show that lethal P. vinckei infection (PvAS) in AKR mice is characterized by increased parasite growth, decreased production of pro-inflammatory cytokines, and attenuated cell proliferation and nitric oxide (NO) synthesis resulting in increased parasitemia which ultimately leads to death of all animals by day 5 post infection. In contrast, AKR mice infected with lethal parasite (PvAR) showed elevated levels of pro-inflammatory cytokines, heightened cell proliferation, and NO synthesis leading to complete parasite clearance by day 22 post infection. Flow cytometric analysis performed on splenocytes from PvAS- and PvAR-infected mice shows that host immunity is severely compromised in PvAS-infected mice as was evident by decreased percentages of CD4(+) and CD8(+) T cells, B cells, plasma cells, dendritic cells (DCs), and macrophages (MΦs) which was in complete contrast to PvAR-infected animals which exhibited elevated numbers of all the cell types analyzed. Taken together, findings of the present study show that coordinated actions of pro-inflammatory cytokines and other immune effector cells are essential to control lethal malarial infection and their attenuation leads to increased parasite growth and, ultimately, death of animals.
authors.affiliation: Division of Parasitology, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, Uttar Pradesh, 226031, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Bhardwaj
authors.forename: Arif Jamal
authors.initials: AJ
authors.lastname: Siddiqui
authors.forename: Manish
authors.initials: M
authors.lastname: Goyal
authors.forename: Kirtika
authors.initials: K
authors.lastname: Prakash
authors.forename: Awakash
authors.initials: A
authors.lastname: Soni
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Puri
authors.forename: Mrigank
authors.initials: M
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D001402:B-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells; D008264:Macrophages / Q000276:immunology; D008288:Malaria / Q000276:immunology* / Q000401:mortality / Q000469:parasitology*; D051379:Mice; D008806:Mice, Inbred AKR; D018512:Parasitemia / Q000276:immunology; D010961:Plasmodium / Q000145:classification* / Q000276:immunology
chemical_list: D016207:Cytokines