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Altered levels of memory T cell subsets and common ?c cytokines in Strongyloides stercoralis infection and partial reversal following anthelmintic treatment.

ABSTRACT: CD4+ and CD8+ T cells are central players in immunity to helminth infections. However, the role of T cell subsets in human helminth infections is not well understood. In addition, the common ?c cytokines, IL-2, IL-4, IL-7, IL-9 and IL-15 play an important role in the maintenance of these CD4+ and CD8+ T cell subsets.To examine the major T cell subsets and their association with the common ?c cytokines, the absolute numbers of CD4+ and CD8+ naïve, central memory, effector memory and effector cells and the plasma levels of IL-2, IL-4, IL-7, IL-9 and IL-15 were measured in Strongyloides stercoralis (Ss) infected (INF, n = 60), helminth-uninfected (UN, n = 58) and in post treatment INF individuals.Ss infection is characterized by significantly increased absolute numbers of naïve and decreased absolute numbers of central and effector memory CD4+ T cells in comparison to UN individuals. No significant difference in the numbers of CD8+ T cell subsets was observed between the groups. The numbers of naïve cells and central memory CD4+ T cells were significantly reversed after anthelmintic treatment. Circulating levels of IL-2, IL-7 and IL-15 were significantly diminished, whereas the levels of IL-4 and IL-9 were significantly increased in INF compared to UN individuals. Following anthelminthic treatment, IL-2, IL-7 and IL-15 levels were significantly increased, while IL-4 and IL-9 levels were significantly decreased. Our data also showed a significant positive correlation between the levels of IL-7 and the numbers of central and effector memory CD4+ T cells.Ss infection is characterized by alterations in the absolute numbers of CD4+ T cell subsets and altered levels of common ?c cytokines IL-2, IL-4, IL-7, IL-9 and IL-15; alterations which are partially reversed after anthelmintic treatment.

SUBMITTER: Rajamanickam A

PROVIDER: S-EPMC5991401 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Altered levels of memory T cell subsets and common γc cytokines in Strongyloides stercoralis infection and partial reversal following anthelmintic treatment.

Rajamanickam Anuradha A Munisankar Saravanan S Bhootra Yukti Y Dolla Chandra Kumar CK Thiruvengadam Kannan K Nutman Thomas B TB Babu Subash S

PLoS neglected tropical diseases 20180524 5

<h4>Background</h4>CD4+ and CD8+ T cells are central players in immunity to helminth infections. However, the role of T cell subsets in human helminth infections is not well understood. In addition, the common γc cytokines, IL-2, IL-4, IL-7, IL-9 and IL-15 play an important role in the maintenance of these CD4+ and CD8+ T cell subsets.<h4>Methods</h4>To examine the major T cell subsets and their association with the common γc cytokines, the absolute numbers of CD4+ and CD8+ naïve, central memory ...[more]

PMID: 29795573

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Project description:BACKGROUND: Differences between noninfective first-stage (L1) and infective third-stage (L3i) larvae of parasitic nematode Strongyloides stercoralisat the molecular level are relatively uncharacterized. DNA microarrays were developed and utilized for this purpose. METHODS AND FINDINGS: Oligonucleotide hybridization probes for the array were designed to bind 3571 putative mRNA transcripts predicted by analysis of 11,335 expressed sequence tags (ESTs) obtained as part of the Nematode EST project. RNA obtained from S. stercoralis L3i and L1 was co-hybridized to each array after labeling the individual samples with different fluorescent tags. Bioinformatic predictions of gene function were developed using a novel cDNA Annotation System software. We identified 967 differentially expressed genes (457 L3i-biased; 510 L1-biased) having greater than two-fold expression differences and p < 0.01. Based on functional analysis, L1s have a larger number of genes putatively involved in transcription (p = 0.0158), and L3is have higher expression of stress-related genes (such as putative heat shock proteins dnj-12, daf-21, dnj-10). Genes with products that have been shown to be immunoreactive in S. sterocoralis-infected humans (SsIR and NIE) were additionally found to be L3i biased. Unique and abundant L3i contigs of interest included S. stercoralis orthologs of cytochrome oxidase ucr 2.1, daf-12, and daf-21, which may be potential chemotherapeutic targets. The S. stercoralis ortholog of fatty acid and retinol binding protein-1, successfully used in a vaccine against Ancylostoma ceylanicum, was identified among the top 25 most L3i-biased genes. The sperm-containing glycoprotein domain, utilized in a vaccine against the nematode Cooperia punctata, was exclusively found in the L3i group and may be a valuable S. stercoralis target of interest. Conclusions A new DNA microarray tool for the examination of S. stercoralis biology has been developed and provides new and valuable insights regarding differences between infective and noninfective S. stercoralis larvae. Potential therapeutic and vaccine targets were identified for further study.

Dataset Information

Altered levels of memory T cell subsets and common ?c cytokines in Strongyloides stercoralis infection and partial reversal following anthelmintic treatment.

Publications

Altered levels of memory T cell subsets and common γc cytokines in Strongyloides stercoralis infection and partial reversal following anthelmintic treatment.

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