Defective antigen-presenting cell function in human neonates

Velilla, Paula A.; Rugeles, Marı́a Teresa; Chougnet, Claire

doi:10.1016/j.clim.2006.08.010

Cited by 153 publications

(143 citation statements)

References 93 publications

(116 reference statements)

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“…The maturation of the immune system, initiated within the fetus, is highly dynamic in character and mutates over time through the first neonatal months and into childhood (Newburg and Walker, 2007). Neonates have low expression of co-stimulatory molecules, diminished dendritic cell (DC) differentiation, impaired phagocytosis as well as defective interaction between DCs, T lymphocytes and regulatory T cells and impaired cytotoxic activity of T cells (Kotiranta-Ainamo et al, 2004;Velilla et al, 2006). Furthermore, the activity of the transplacentally derived maternal immunoglobulin G antibodies results in a deficiency of specific humoral responses, which include minimal levels of IgA in neonates (Keles et al, 2010).…”

Section: Microbes and Immunitymentioning

confidence: 99%

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

Dinan

Cryan

2016

Neuropsychopharmacol

201

121

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There is now a large volume of evidence to support the view that the immune system is a key communication pathway between the gut and brain, which plays an important role in stress-related psychopathologies and thus provides a potentially fruitful target for psychotropic intervention. The gut microbiota is a complex ecosystem with a diverse range of organisms and a sophisticated genomic structure. Bacteria within the gut are estimated to weigh in excess of 1 kg in the adult human and the microbes within not only produce antimicrobial peptides, short chain fatty acids, and vitamins, but also most of the common neurotransmitters found in the human brain. That the microbial content of the gut plays a key role in immune development is now beyond doubt. Early disruption of the host-microbe interplay can have lifelong consequences, not just in terms of intestinal function but in distal organs including the brain. It is clear that the immune system and nervous system are in continuous communication in order to maintain a state of homeostasis. Significant gaps in knowledge remain about the effect of the gut microbiota in coordinating the immune-nervous systems dialogue. However, studies using germ-free animals, infective models, prebiotics, probiotics, and antibiotics have increased our understanding of the interplay. Early life stress can have a lifelong impact on the microbial content of the intestine and permanently alter immune functioning. That early life stress can also impact adult psychopathology has long been appreciated in psychiatry. The challenge now is to fully decipher the molecular mechanisms that link the gut microbiota, immune, and central nervous systems in a network of communication that impacts behavior patterns and psychopathology, to eventually translate these findings to the human situation both in health and disease. Even at this juncture, there is evidence to pinpoint key sites of communication where gut microbial interventions either with drugs or diet or perhaps fecal microbiota transplantation may positively impact mental health.

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Section: Microbes and Immunitymentioning

confidence: 99%

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

Dinan

Cryan

2016

Neuropsychopharmacol

201

121

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“…However, it is unlikely that the approximately 14% of European ancestry individuals heterozygous for the glutamine allele harbor significant immunodeficiencies, and therefore these individuals provide a unique opportunity to better understand the lifelong, dynamic host-intestinal microbial interactions that are the key to IBD. We are born with a sterile intestine [25] and an immature immune system [128] , with the rapid acquisition of intestinal flora evolving dynamically with early instruction signals to the host immune response. The significant susceptibility of neonates to infection may correlate with their incapacity to induce IL-12p35 with lipopolysaccharide stimulation [129] , with IL-23p19 induction being largely intact [130] .…”

Section: Il23r Is Associated With CD and Ucmentioning

confidence: 99%

Inflammatory bowel disease: Genetic and epidemiologic considerations

Cho

2008

WJG

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Genome-wide association studies have firmly established that many genomic loci contribute to inflammatory bowel disease, especially in Crohn's disease. These studies have newly-established the importance of the interleukin 23 and autophagy pathways in disease pathogenesis. Future challenges include: (1) the establishment of precisely causal alleles, (2) definition of altered functional outcomes of associated and causal alleles and (3) integration of genetic findings with environmental factors.

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“…Consequently, preterm neonates mostly have diminished monocyte counts [1,4,5,13,14] . However, in contrast to the extensively studied major population of classical CD14 bright monocytes, little knowledge exists on Fc γ receptor III positive (i.e., CD16 bright ) monocytes in neonates.…”

Section: Introductionmentioning

confidence: 99%

Diminished HLA-DR expression on monocyte and dendritic cell subsets indicating impairment of cellular immunity in pre-term neonates: a prospective observational analysis

Schefold¹,

Porz

Uebe

et al. 2015

Journal of Perinatal Medicine

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Aims: The risk of neonates for severe infection/sepsis is reciprocally proportional to gestational age and birth weight. As monocytes and dendritic cells (DC) are recognised key antigen-presenting immune cells, we aimed to elucidate whether neonatal age is associated with reduced expression of human-leukocyte antigen-DR (HLA-DR) antigens on subsets of monocytes and DCs. Methods: Forty-three consecutive neonates (20 male, mean gestational age 236.0 ± 26.8 days; mean 1-min Apgar score 7.5 ± 2.0) were included in a monocentric prospective observational analysis. Patients were grouped according to gestational age (n = 15 full-term, n = 28 pre-term defined as < 33 weeks). Ten healthy adult volunteers were assessed also. Flow-cytometric assessment of HLA-DR expression was performed in subsets of peripheral blood myeloid and plasmacytoid DCs (MDC and PDC) and monocytes (CD14 bright-CD16 negative /CD14 positive CD16 positive /CD14 dim CD16 positive ). Clinical and routine laboratory data were followed up. Results: At birth, leukocyte counts were increased in full-term neonates. Monocyte counts were significantly increased in neonates when compared with adults (all P < 0.05). A significant numerical increase of CD14 bright-CD16 negative and CD14 positive CD16 positive monocytes was noted in pre-term and full-term neonates (all P < 0.05), while HLA-DR expression in these subsets was significantly diminished (most pronounced in pre-term infants, P < 0.0001). MDC and PDC HLA-DR expression was reduced also (all P < 0.05). Clinical indices (e.g., pH, days on antibiotics/mechanical ventilation, fever/sepsis) were not found to correlate with immunological indices. Conclusions: We observed a markedly diminished HLA-DR expression on monocyte and DC subsets in pre-term and full-term neonates, which may contribute to impaired antimicrobial defence mechanisms in the early days of life.

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Defective antigen-presenting cell function in human neonates

Cited by 153 publications

References 93 publications

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

Inflammatory bowel disease: Genetic and epidemiologic considerations

Diminished HLA-DR expression on monocyte and dendritic cell subsets indicating impairment of cellular immunity in pre-term neonates: a prospective observational analysis

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