Proinflammatory responses and higher IL-10 production by T cells correlate with protection against malaria during pregnancy and delivery outcomes.
Pregnancy triggers immunological changes aimed to tolerate the fetus. However, it has not been properly addressed whether similar changes occur in tropical areas with high infection pressure and whether these changes render women more susceptible to infectious diseases. We compared the frequencies of T cell subsets, including regulatory T cells, in pregnant and nonpregnant women from Papua New Guinea, a high malaria transmission area, and from Spain, a malaria-free country. We also assessed the relationship among these cellular subsets, malaria infection, and delivery outcomes. CD4(+)FOXP3(+)CD127(low) T cells (Tregs) were decreased in pregnant women in both countries but were not associated with malaria infection or poor delivery outcomes. An expansion of IFN-γ-producing cells and intracytoplasmic IFN-γ levels was found in pregnant compared with nonpregnant women only in Papua New Guinea. Increased CD4(+)IL-10(+)IFN-γ(+) frequencies and Treg-IFN-γ production were found in women with current Plasmodium falciparum infection. Higher CD4(+)IL-10(-)IFN-γ(+) T cells frequencies and production of proinflammatory cytokines (including TNF and IL-2) at recruitment (first antenatal visit) had a protective association with birth weight and future (delivery) P. falciparum infection, respectively. Higher intracellular IL-10 levels in T cells had a protective association with future P. falciparum infection and hemoglobin levels at delivery. The protective associations were found also with nonmalaria-specific T cell responses. Treg frequencies positively correlated with plasma eotaxin concentrations, but this subset did not express eotaxin receptor CCR3. Thus, an activated immune system during pregnancy might contribute to protection against malaria during pregnancy and poor delivery outcomes.
Malaria Program, Barcelona Centre for International Health Research, Hospital Clínic-University of Barcelona, 08036 Barcelona, Spain; Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom; pilar.requena@cresib.cat.
Pilar
P
Requena
Malaria Program, Barcelona Centre for International Health Research, Hospital Clínic-University of Barcelona, 08036 Barcelona, Spain;
Diana
D
Barrios
Vector Borne Disease Unit, Papua New Guinea Institute of Medical Research, Madang 511, Papua New Guinea; Infection and Immunity Division, Walter and Eliza Hall Institute, Parkville, Victoria 3050, Australia;
Leanne J
LJ
Robinson
Vector Borne Disease Unit, Papua New Guinea Institute of Medical Research, Madang 511, Papua New Guinea;
Paula
P
Samol
Department of Medicine, University of Melbourne, Parkville, Victoria 3050, Australia;
Alexandra J
AJ
Umbers
Vector Borne Disease Unit, Papua New Guinea Institute of Medical Research, Madang 511, Papua New Guinea;
Regina
R
Wangnapi
Vector Borne Disease Unit, Papua New Guinea Institute of Medical Research, Madang 511, Papua New Guinea;
Maria
M
Ome-Kaius
Vector Borne Disease Unit, Papua New Guinea Institute of Medical Research, Madang 511, Papua New Guinea;
Anna
A
Rosanas-Urgell
Malaria Program, Barcelona Centre for International Health Research, Hospital Clínic-University of Barcelona, 08036 Barcelona, Spain;
Alfredo
A
Mayor
Department of Maternal-Fetal Medicine, Hospital Clinic-August Pi i Sunyer Biomedical Research Institute, Centre for Biomedical Network Research in Rare Diseases, 08028 Barcelona, Spain;
Marta
M
López
Malaria Program, Barcelona Centre for International Health Research, Hospital Clínic-University of Barcelona, 08036 Barcelona, Spain;
Elisa
E
de Lazzari
Malaria Program, Caucaseco Scientific Research Center, 76001000 Cali, Colombia;
Myriam
M
Arévalo-Herrera
Malaria Program, Barcelona Centre for International Health Research, Hospital Clínic-University of Barcelona, 08036 Barcelona, Spain;
Carmen
C
Fernández-Becerra
Malaria Program, Barcelona Centre for International Health Research, Hospital Clínic-University of Barcelona, 08036 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain; and.
Hernando
H
del Portillo
Malaria Program, International Center for Genetic Engineering and Biotechnology, Delhi 110 067, India.
Chetan E
CE
Chitnis
Vector Borne Disease Unit, Papua New Guinea Institute of Medical Research, Madang 511, Papua New Guinea;
Peter M
PM
Siba
Department of Medicine, University of Melbourne, Parkville, Victoria 3050, Australia;
Stephen
S
Rogerson
Malaria Program, Barcelona Centre for International Health Research, Hospital Clínic-University of Barcelona, 08036 Barcelona, Spain; Infection and Immunity Division, Walter and Eliza Hall Institute, Parkville, Victoria 3050, Australia;
Ivo
I
Mueller
Malaria Program, Barcelona Centre for International Health Research, Hospital Clínic-University of Barcelona, 08036 Barcelona, Spain;
Azucena
A
Bardají
Malaria Program, Barcelona Centre for International Health Research, Hospital Clínic-University of Barcelona, 08036 Barcelona, Spain;
Clara
C
Menéndez
Malaria Program, Barcelona Centre for International Health Research, Hospital Clínic-University of Barcelona, 08036 Barcelona, Spain;
Carlota
C
Dobaño
D000328:Adult; D000954:Antigens, Surface / Q000378:metabolism; D016022:Case-Control Studies; D018925:Chemokines / Q000097:blood / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D018655:Lymphocyte Count; D008288:Malaria / Q000276:immunology* / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic; D011256:Pregnancy Outcome; D012307:Risk Factors; D013030:Spain; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D055815:Young Adult
D000954:Antigens, Surface; D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D016753:Interleukin-10