Postnatal maturation of innate immune functions in human infants: effects of natural versus therapeutic exposure to microbial stimuli — ASN Events
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  2. Poster Session Three
  3. Postnatal maturation of innate immune functions in human infants: effects of natural versus therapeutic exposure to microbial stimuli

Postnatal maturation of innate immune functions in human infants: effects of natural versus therapeutic exposure to microbial stimuli (#392)

Niamh M Troy 1 , Julie Varghese 2 , Emmanuelle Fantino 2 , Diana Gutierrez Cardenas 2 , Michael Serralha 1 , Barbara Holt 1 , Anthony Bosco 1 , Deborah Strickland 1 , Peter Sly 2 , Patrick Holt 1
  1. Telethon kids Institute, The University of Western Australia, Subiaco, WA, Australia
  2. Child Health Research Centre, The University of Queensland, Brisbane, Australia

Background:Severe lower respiratory tract infections (sLRTIs) are important causes of hospitalisation in infants, constituting major risk factors for asthma development. We are participating in a clinical trial testing the bacterial-derived immunomodulator OM-85 as a potential preventive treatment to reduce infection frequency/severity in infants. The trial is based on the hypothesis that increased sLRI risk in infants is related to the functional immaturity of their immune systems, and that OM-85 treatment can accelerate functional maturation. Our focus is the mechanism-of-action of OM-85 on innate immune functions associated with resistance to infection, and the effects of infections themselves on postnatal maturation of these functions.

Aims:(i) to elucidate the effects of continuous treatment of infants during their first winter with OM-85 on maturation of innate immune function(s), (ii) to identify the key innate immune defence pathways which are responsible for their high-risk for infection, (iii) to determine the effects of natural infections on immune maturation.

Method:The study population consists of children age 3-9 months given OM-85 orally (n=22) during the first winter of life, and matched placebo controls (n=25). PBMC were collected at the beginning and end of the 5 month treatment period. Cellular profiling has been performed on PBMC by flow cytometry to elucidate the phenotypic properties, and to determine the effect of treatment on cellular subsets. PBMC were stimulated in-vitro with LPS (inflammatory bacterial challenge), PolyI:C (viral mimic) and PHA (T-cell stimulant) and genome-wide responses were profiled by RNAseq. Inflammatory responses were measured in culture supernatants at the protein-level, and we are utilising systems-level analysis to elucidate microbial exposure effects on underlying gene networks.

Expected Outcomes:We hope to advance our current understanding of the drivers of immune maturation during infancy to contribute towards the development of novel therapeutic strategies for protection of infants against the detrimental effects of sLRTIs.

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