Innate Immunity to Respiratory Infection in Early Life

Abstract

Early life is a period of particular susceptibility to respiratory infections and symptoms are frequently more severe in infants than in adults. The neonatal immune system is generally held to be deficient in most compartments; responses to innate stimuli are weak, antigen-presenting cells have poor immunostimulatory activity and adaptive lymphocyte responses are limited, leading to poor immune memory and ineffective vaccine responses. For mucosal surfaces such as the lung, which is continuously exposed to airborne antigen and to potential pathogenic invasion, the ability to discriminate between harmless and potentially dangerous antigens is essential, to prevent inflammation that could lead to loss of gaseous exchange and damage to the developing lung tissue. We have only recently begun to define the differences in respiratory immunity in early life and its environmental and developmental influences. The innate immune system may be of relatively greater importance than the adaptive immune system in the neonatal and infant period than later in life, as it does not require specific antigenic experience. A better understanding of what constitutes protective innate immunity in the respiratory tract in this age group and the factors that influence its development should allow us to predict why certain infants are vulnerable to severe respiratory infections, design treatments to accelerate the development of protective immunity, and design age specific adjuvants to better boost immunity to infection in the lung.

Innate Immune Evasion by Human Respiratory RNA Viruses

“…Arguably, the innate immune system is more important in early life, when the adaptive functions are still underdeveloped [14]. Yet, the young infant is probably exposed to as many incoming pathogens as older children and adults are, so the innate immune system plays a very important role in the protection from respiratory infection in young children.…”

“…The fact that respiratory infections are one of the leading causes of mortality in children under 5 years of age [18,19] suggests that the interactions of the (innate) immune responses in the infant respiratory tract with incoming pathogens is indeed a delicate one, and the balance between severe illness and overcoming an infection may be relatively easily tipping towards the dangerous side. That the innate immune response plays an important role in defense against respiratory infections in early life may be further illustrated by the fact that severe RSV infections in children are linked with polymorphisms in genes encoding innate immune factors (reviewed in [14,20]). Also later in life, the innate immune system plays an important role in the response against respiratory viruses (reviewed in [1]), and in the lungs these first responses against incoming viruses are governed primarily by alveolar and interstitial macrophages, DCs, airway epithelial cells, innate lymphocytes, and neutrophils.…”

“…To facilitate comparison between the respiratory viruses described here, known and arguably important innate immune evasion strategies are listed, and for each strategy it is discussed how each virus group exploits its own mechanism. Innate immune evasion obviously links to the innate immune responses that are known to be elicited by respiratory and other (RNA) viruses, and while this will be elaborated to a limited extent below, they have also been reviewed comprehensively in recent reviews by others [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17].…”

First Pediatric Case of Coronavirus Disease 2019 in Korea

“…Meanwhile, the role of innate immunity to respiratory tract infection is greater in early life because the adaptive immune response is underdeveloped in young children. 10 Given that both young children and adults lack adaptive specific immunity to this novel virus, mild clinical course in young children may be explained by their dominant innate immune response compared to adults. Weaker ability to trigger an acute inflammatory response to SARS-CoV-2 might also contribute to the children's better outcome.…”

Characterisation of morphological differences in well-differentiated nasal epithelial cell cultures from preterm and term infants at birth and one-year

“…(14) Furthermore, encounters with pathogens during the crucial period of neonatal development may have long term impacts on future respiratory health. (15) For instance, it is known that severe RSV infection during early infancy is linked to later diagnosis of wheeze and asthma(16,17) and even later life respiratory diseases, such as chronic obstructive pulmonary diseases (COPD), may be associated with early life experiences. (4) Therefore, given the current limited knowledge of the development of early AEC immune responses, greater understanding of these responses is needed to yield novel insights into the mechanisms of susceptibility underpinning childhood airway disease.…”