An Evaluation of the Neonatal Immune System Using a <i>Listeria</i> Infection Model

Abstract

Background: T helper 1 (Th1)/T helper 2 (Th2)-biased cytokine regulation may be another reason that neonates are much more susceptible to infectious disease than are adults. Objectives: We attempted to determine the ability of neonatal mice to direct the Th1 phenotype against Listeria monocytogenes (LM), because LM, an intracellular Gram-positive bacterium, induces profound cellular immunity by Th1 cells in vivo. Methods: In order to determine whether neonatal mice evidence strong Th1 activity during LM infection, neonatal mice were compared with adult mice with regard to susceptibility to LM, cytotoxic T lymphocyte activity, and cytokine profiles. Neonatal gene profiles relevant to Th1 and Th2 differentiation during LM infection were also compared between neonatal and adult mice, via real-time PCR and RT-PCR. Results: Neonatal mice were found to be far more susceptible to LM infection than adult mice, due to a lack in the induction of cytotoxic T cell activity, coupled with poor IFN-γ secretion. Further, LM-infected neonatal mice evidenced much lower levels of expression of Th1-type immune components, including IL-12, IFN-γ, Delta-4 and T-bet, as compared to those features in adult mice. These results may be due to the comparably lower expressions of mannose-bind lectins and some of toll-like receptors (TLRs) such as TLR-5, -6 and -9, necessary mediators to develop Th1 immune responses. Conclusions: Neonatal mice may not mount an adequate Th1 type immune response due to a significantly lower expression of Th1-type immune components as compared to adult mice, even when forced into a Th1-prone environment.

Delaying BCG vaccination from birth to 10 weeks of age may result in an enhanced memory CD4 T cell response

“…Very limited data on “maturation” of the infant immune response over the first few months of life exists, but factors that may have contributed include inefficient antigen presenting cell function, including limited capacity to produce IL-12 [37], a critical cytokine for inducing the Th1 responses characteristic of successful mycobacterial immunity. In addition, animal and human evidence suggests that the newborn’s immune system is skewed towards a Th2 response [38–40], which may suppress induction of Th1 immunity.…”

Maturation of the enteric mucosal innate immune system during the postnatal period

“…Its major entry port is the intestinal epithelium followed by spread to systemic organs . The increased susceptibility of neonates results from an impaired cytotoxic T‐lymphocyte response caused by increased levels of serum IL‐10 and reduced IFN‐γ, reflecting the Th2‐biased immune response of the neonate immune system discussed above . Reduced IFN‐γ production might also contribute to the enhanced risk for infection with the enteropathogens Salmonella enterica non‐typhoidal and Cryptosporidium parvum .…”

Potential of immunomodulatory agents for prevention and treatment of neonatal sepsis

“…Neonatal immune responses are generally T H 2-skewed, being geared towards immune tolerance instead of towards defense from microbial infections [T H 1 skewed] (Table 1) 7–10 . Neonatal antigen-presenting cells (APCs) demonstrate impaired production of T H 1-polarizing cytokines (e.g., IL-12, interferon-γ that direct immune responses against microbial pathogens) and impaired up-regulation of co-stimulatory molecules to most Toll-like receptor (TLR) agonists 2,11,12 . Nevertheless, certain stimuli such as Bacille Calmette Guerin (BCG) induce adult-like responses via mechanisms that are not yet completely defined 7,13,14 .…”