Study Suggests Lower Plasmacytoid Dendritic Cell (pDC) Activity May Be Associated With Increased Risk of Developing the Common Cold

Background and Objectives

Upper respiratory tract infections such as the common cold are generally self-limiting; however, they place a burden on both individuals and society through reduced quality of life and absenteeism from work or school. Furthermore, although susceptibility to infectious diseases varies considerably among individuals even under similar living conditions, validated methods for predicting individual susceptibility before infection remain limited.
Plasmacytoid dendritic cells (pDCs) are immune cells that play a central role in antiviral immunity and are the principal producers of type I interferons, including IFN-α. Despite their importance in host defense against viral infections, evidence linking individual differences in pDC function to subsequent risk of developing the common cold remains limited.
Therefore, we investigated whether IFN-α production induced by a TLR9 agonist at baseline, used as a functional surrogate marker of pDC activity, was associated with the occurrence of the common cold during the subsequent four-week observation period.

Study Design and Methods

This prospective observational analysis*3 utilized data obtained from participants in the placebo arm of a previous clinical study involving healthy medical students in Vietnam. The present analysis included 41 participants for whom both baseline IFN-α production data and information on common cold incidence during the observation period were available.
Peripheral blood mononuclear cells (PBMCs)*4 were isolated from blood samples collected at baseline. The cells were stimulated with CpG oligodeoxynucleotide (CpG ODN)*5, a TLR9 agonist that mimics microbial DNA signals, and IFN-α production was measured after 24 hours of culture.
Participants were then classified according to the amount of IFN-α produced into a HIGH group (n = 20) and a LOW group (n = 21), based on the median IFN-α production level.*6
During the four-week observation period, participants recorded their body temperature and seven cold-related symptoms daily: runny nose, plugged nose, sneezing, sore throat, cough, head congestion, and fatigue. A common cold event was defined*7 as the presence of fever (≥37.5°C) together with a symptom score exceeding a predefined threshold.
Associations between baseline pDC activity and subsequent occurrence of the common cold and individual cold symptoms were analyzed.
Importantly, under the stimulation conditions used in this study, intracellular staining confirmed that the vast majority of IFN-α-producing cells within PBMCs were pDCs (mean: 97.2%).

*3 Secondary analysis of data collected in the previous study: Effects of Lactococcus lactis Strain Plasma (LC-Plasma) Intake on Infection-Related Symptoms Among Healthcare Workers: A Randomized, Double-Blind, Placebo-Controlled Study
*4 A collective term for immune cells circulating in the blood, including pDCs and lymphocytes.
*5 A synthetic DNA sequence that mimics characteristic microbial DNA motifs recognized by TLR9.
*6 Participants were classified into HIGH and LOW groups using the median baseline IFN-α production level.
*7 Based on the definition used in: Randomized Controlled Trial of Nasal Thermotherapy for the Treatment of the Common Cold: A Feasibility Study | BMJ Open

Key Findings

1. Participants with lower pDC activity showed a higher risk of developing the common cold

During the four-week observation period, seven of the 21 participants in the LOW group developed a common cold, whereas no cases were observed among the 20 participants in the HIGH group. The risk of developing a common cold was higher in the LOW group.

2. Higher risks of fever, plugged nose, and sore throat were observed in the LOW group

Participants in the LOW group also exhibited higher risks of fever (≥37.5°C), plugged nose, and sore throat compared with those in the HIGH group.

Significance of the Findings

A key strength of this study is its prospective design, which enabled evaluation of the association between IFN-α production capacity measured before the observation period and subsequent occurrence of the common cold.
The findings suggest that individuals with lower pDC activity, as reflected by reduced IFN-α production capacity, may be more susceptible to upper respiratory tract infections, including the common cold, over the short term. These results provide further evidence linking innate immune function to individual differences in susceptibility to respiratory infections.

Future Outlook

Future studies will expand both the study population and observation period to further investigate the relationship between innate immune functions, including pDC activity and type I interferon responses, and susceptibility to infectious diseases. These findings may contribute to the development of personalized infection-prevention approaches and improved immune health management.