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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Maturation of innate responses to mycobacteria over the first nine months of life
Journal of Immunology, Volume 192, No. 10, Year 2014
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Description
Newborns and young infants are particularly susceptible to infections, including Mycobacterium tuberculosis. Further, immunogenicity of vaccines against tuberculosis and other infectious diseases appears suboptimal early in life compared with later in life. We hypothesized that developmental changes in innate immunity would underlie these observations. To determine the evolution of innate responses to mycobacteria early in life, whole blood or PBMC from newborns, as well as 10- and 36-wk-old infants, was incubated with viable Mycobacterium bovis bacillus Calmette-Guérin or TLR ligands. Innate cell expression of cytokines and maturation markers was assessed, as well as activation of the proinflammatory NF-kB- and MAPK-signaling pathways. Bacillus Calmette-Guérin-induced production of the proinflammatory cytokines TNF-a, IL-6, and IL-12p40 increased from the newborn period to 9 mo of age in monocytes but not in myeloid dendritic cells. No changes in production of anti-inflammatory IL-10 were observed. CD40 expression increased with age in both cell populations. Older infants displayed substantial activation of all three signal transduction molecules: degradation of NF-kB inhibitor IkBa and phosphorylation of MAPK Erk and p38 upon TLR1/2 triggering, compared with predominant activation of only one of any of these molecules in newborns. Maturation of innate proinflammatory responses during the first 9 mo of life may underlie more effective control of mycobacteria and other pathogens observed later in infancy and age-related differential induction of Th1 responses by vaccination. Copyright © 2014 by The American Association of Immunologists, Inc.
Authors & Co-Authors
Shey, Muki Shehu
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Nemes, Elisa
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
Whatney, Wendy E.
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
de Kock, Marwou
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
Africa, Hadn
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
Barnard, Charlene
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
van Rooyen, Michele
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
Stone, Lynnette
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
Riou, Catherine
South Africa, Cape Town
University of Cape Town
Kollmann, Tobias R.
Canada, Vancouver
The University of British Columbia
Hawn, Thomas Richard
United States, Seattle
University of Washington School of Medicine
Scriba, Thomas J.
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
Hanekom, Willem Albert
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
Statistics
Citations: 32
Authors: 13
Affiliations: 5
Identifiers
Doi:
10.4049/jimmunol.1400062
ISSN:
00221767
e-ISSN:
15506606