0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Review |

Influenza A Virus Infection, Innate Immunity, and Childhood

Bria M. Coates, MD1,2; Kelly L. Staricha1; Kristin M. Wiese, MD3; Karen M. Ridge, PhD3,4
[+] Author Affiliations
1Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois
2Division of Critical Care Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois
3Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
4Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois
JAMA Pediatr. 2015;169(10):956-963. doi:10.1001/jamapediatrics.2015.1387.
Text Size: A A A
Published online

Infection with influenza A virus is responsible for considerable morbidity and mortality in children worldwide. While it is apparent that adequate activation of the innate immune system is essential for pathogen clearance and host survival, an excessive inflammatory response to infection is detrimental to the young host. A review of the literature indicates that innate immune responses change throughout childhood. Whether these changes are genetically programmed or triggered by environmental cues is unknown. The objectives of this review are to summarize the role of innate immunity in influenza A virus infection in the young child and to highlight possible differences between children and adults that may make children more susceptible to severe influenza A infection. A better understanding of age-related differences in innate immune signaling will be essential to improve care for this high-risk population.

Figures in this Article

Figures

Place holder to copy figure label and caption
Figure 1.
Prevalence of Comorbid Conditions Among Patients Requiring Hospitalization for Influenza A Virus Infection During the 2012-2013 Influenza Season

Children who were hospitalized with influenza were significantly less likely to have had a preexisting medical condition before their hospitalization compared with the adult population. Data are adapted from the Centers for Disease Control and Prevention FluView website.5

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
How The Innate Immune Response to Influenza A Virus (IAV) Infection May Differ Between Children and Adults

Viral RNA is recognized by Toll-like receptors located in the endosome, primarily TLR3 and TLR7, which activate the adaptor proteins Toll/interleukin (IL)–1 receptor domain–containing adapter-inducing interferon β (TRIF) and myeloid differentiation primary response gene 88 (MyD88), respectively. Activated TRIF and MyD88 act downstream on interferon regulatory factor 3 (IRF3), IRF7, and nuclear factor κB (NF-κB). Activated IRF3 and IRF7 translocate to the nucleus, where they stimulate transcription of the type I interferons (IFN-α/β). Nuclear factor κB serves as a transcription factor promoting production of proinflammatory cytokines and chemokines, including pro–interleukin-1β (pro–IL-1β), IL-6, IL-10, and IL-12. Alternatively, cytosolic viral RNA is recognized by retinoic acid–inducible gene I (RIG-I), which binds to its adaptor mitochondrial antiviral signaling protein (MAVS), stimulating IRF3 and NF-κB and their downstream transcription products IFN-α/β and proinflammatory cytokines. Nuclear factor κB activation, in addition to a second signal indicating cellular stress (changes in intracellular ionic concentrations, reactive oxygen species [ROS], potassium flux, etc), induces assembly of the multimeric nucleotide-binding oligomerization domain (NOD)–like receptor family, pyrin domain–containing 3 (NLRP3) inflammasome protein complex. The NLRP3 inflammasome activates caspase 1, which cleaves the proinflammatory cytokines to release their mature forms. Upward and downward arrows indicate the relative cytokine response in the young pediatric population compared with adults. The overall consequence may move away from a helper T-cell subtype 1 (TH1) response and toward a TH2- and TH17-predominant response that is more effective against extracellular pathogen clearance, leaving the young host at risk for the intracellular influenza pathogen. dsRNA indicates double-stranded RNA; ssRNA, single-stranded RNA. Illustration by Jacqueline Schaffer, MS, medical illustrator.

Graphic Jump Location

Tables

References

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

1,069 Views
0 Citations
×

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
Jobs
brightcove.createExperiences();