Early-life respiratory infections and developmental immunity determine lifelong lung health

Lloyd, Clare M.; Saglani, Sejal

doi:10.1038/s41590-023-01550-w

Cited by 10 publications

(6 citation statements)

References 68 publications

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“…Our study does not rule out that microbes regulate allergic inflammation, because there is incontrovertible evidence that they can exert such effects. Some intestinal nematode infections and gut and lung commensals have been shown to dampen allergic inflammation (56)(57)(58). Thus, perhaps, microbes with important antiinflammatory functions were absent from our wildling colony.…”

Section: Discussionmentioning

confidence: 96%

Laboratory mice with a wild microbiota generate strong allergic immune responses

Ma,

Urgard,

Runge

et al. 2023

Sci. Immunol.

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Allergic disorders are caused by a combination of hereditary and environmental factors. The hygiene hypothesis postulates that early-life microbial exposures impede the development of subsequent allergic disease. Recently developed “wildling” mice are genetically identical to standard laboratory specific pathogen–free (SPF) mice but are housed under seminatural conditions and have rich microbial exposures from birth. Thus, by comparing conventional SPF mice with wildlings, we can uncouple the impact of lifelong microbial exposures from genetic factors on the allergic immune response. We found that wildlings developed larger populations of antigen-experienced T cells than conventional SPF mice, which included interleukin-10–producing CD4 T cells specific for commensal Lactobacilli strains and allergy-promoting T helper 2 (T H 2) cells. In models of airway exposure to house dust mite (HDM), recombinant interleukin-33, or Alternaria alternata , wildlings developed strong allergic inflammation, characterized by eosinophil recruitment, goblet cell metaplasia, and antigen-specific immunoglobulin G1 (IgG1) and IgE responses. Wildlings developed robust de novo T H 2 cell responses to incoming allergens, whereas preexisting T H 2 cells could also be recruited into the allergic immune response in a cytokine-driven and TCR-independent fashion. Thus, wildling mice, which experience diverse and lifelong microbial exposures, were not protected from developing pathological allergic immune responses. Instead, wildlings mounted robust allergic responses to incoming allergens, shedding new light on the hygiene hypothesis.

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Section: Discussionmentioning

confidence: 96%

Laboratory mice with a wild microbiota generate strong allergic immune responses

Ma,

Urgard,

Runge

et al. 2023

Sci. Immunol.

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“…We delivered probiotics within 24 h of birth, aiming to modulate respiratory health. Loyd and Saglani [11] determined in a review that alterations in the respiratory system early in life can determine lifelong lung health. Lima et al [12] showed changes in healthy and diseased calves' upper respiratory tract microbiomes from 3 days of age to 35 days of age.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Probiotics in a Milk Replacer on Leukocyte Differential Counts, Phenotype, and Function in Neonatal Dairy Calves

Eicher,

Kritchevsky,

Bryan

et al. 2023

Microorganisms

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Probiotics have been investigated for many health benefits; however, few studies have been performed to determine the effects of oral probiotics on peripheral blood and respiratory immune cells in cattle. Our objectives were to determine changes in health and growth status, differential blood cell counts and function, and blood and lung cell function using flow cytometry and PCR in dairy calves fed a milk replacer with (PRO, N = 10) or without (CON, N = 10) the addition of probiotics to the milk replacer and dry rations from birth to weaning. Performance and clinical scores were not different between the treatment groups. Treatment-by-day interactions for peripheral blood leukocyte populations differed in cell number and percentages. A greater percentage of leukocytes expressed the cell surface markers CD3, CD4, CD8, CD11b, and CD205 on d 21 in CON animals. Lung lavages were performed on five animals from each treatment group on d 52. There were no differences between treatment groups for the expression of cytokines and Toll-Like Receptors as measured using Polymerase Chain Reaction, possibly due to the small sample size. Oral probiotics appear to affect peripheral blood immune cells and function. Their effect on overall calf health remains to be determined.

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“…The development of human lungs is a complex process that starts in early pregnancy and continues into adulthood, typically until around 20-25 years of age (Figure 3) [15,29]. This intricate timeline involves a plethora of events laying the foundation for a lifetime of respiratory function [30,42].…”

Section: Linking Fetal Lung Development Disorders To Adult Diseasesmentioning

confidence: 99%

“…Stocks et al summarized data showing that factors affecting fetal lung development can disrupt the normal timeline and have a lasting impact on an individual's health [29]. Notably, some papers emphasize the link between chronic lung diseases, a primary source of morbidity and mortality worldwide, and irregularities in fetal lung development [15,29]. The development of the lungs is a continuous process with overlapping stages, as most processes begin at the center and progress towards the periphery.…”

Section: Linking Fetal Lung Development Disorders To Adult Diseasesmentioning

confidence: 99%

“…Nevertheless, this labyrinthine process of lung development can be subjected to disruptions because of different reasons (premature births, complications during pregnancy, undernutrition, infections, etc.) [13][14][15][16], leading to a wide spectrum of disorders affecting lungs not only in childhood but also in adult age [17]. Traditionally, these disorders have been scrutinized primarily for their immediate implications on neonatal health.…”

Section: Introductionmentioning

confidence: 99%

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Association of Fetal Lung Development Disorders with Adult Diseases: A Comprehensive Review

Yaremenko,

Pechnikova,

Porpodis

et al. 2024

JPM

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Fetal lung development is a crucial and complex process that lays the groundwork for postnatal respiratory health. However, disruptions in this delicate developmental journey can lead to fetal lung development disorders, impacting neonatal outcomes and potentially influencing health outcomes well into adulthood. Recent research has shed light on the intriguing association between fetal lung development disorders and the development of adult diseases. Understanding these links can provide valuable insights into the developmental origins of health and disease, paving the way for targeted preventive measures and clinical interventions. This review article aims to comprehensively explore the association of fetal lung development disorders with adult diseases. We delve into the stages of fetal lung development, examining key factors influencing fetal lung maturation. Subsequently, we investigate specific fetal lung development disorders, such as respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), congenital diaphragmatic hernia (CDH), and other abnormalities. Furthermore, we explore the potential mechanisms underlying these associations, considering the role of epigenetic modifications, transgenerational effects, and intrauterine environmental factors. Additionally, we examine the epidemiological evidence and clinical findings linking fetal lung development disorders to adult respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and other respiratory ailments. This review provides valuable insights for healthcare professionals and researchers, guiding future investigations and shaping strategies for preventive interventions and long-term care.

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Early-life respiratory infections and developmental immunity determine lifelong lung health

Cited by 10 publications

References 68 publications

Laboratory mice with a wild microbiota generate strong allergic immune responses

Laboratory mice with a wild microbiota generate strong allergic immune responses

The Effect of Probiotics in a Milk Replacer on Leukocyte Differential Counts, Phenotype, and Function in Neonatal Dairy Calves

Association of Fetal Lung Development Disorders with Adult Diseases: A Comprehensive Review

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