Respiratory pathogens encounter various lines of defenses before infection of the host is established. The innate immune response represents an important first-line protection mechanism against potentially pathogenic microorganisms during early stages of infection of the naive host. Important players in this host defense system are ‘collectins’, a class of soluble innate immune proteins. Well-characterized members of the collectin family are the surfactant proteins A (SP-A) and D (SP-D). These collectins are expressed in the lung and also in extrapulmonary mucosal tissues. Collectins are secreted as multimers resulting in trimeric clustering of the lectin domains which enables recognition of evolutionary conserved sugar patterns present on the surface of a large variety of pathogens. Binding to collectins may lead to direct agglutination and neutralization of pathogens, to opsonization in order to present bound microbes directly to phagocytes, to modulation of the inflammatory response and to regulation of dendritic cell and T cell functions. In pulmonary tissue, this early acute-phase-like response can be regarded as a crucial layer of protection against a vast array of pathogens that escape the physical barriers and threaten to infect the delicate respiratory epithelium. An important clinical application may be the inhalation, or instillation of collectin-based drugs as part of surfactant therapy, to prevent and treat infectious and inflammatory diseases of newborn infants.

Breastfeeding is indicated to support neonatal immune development and to protect against neonatal infections and allergies. Human milk composition is widely studied in relation to these unique abilities, which has led to the identification of various immunomodulating components in human milk, including various bioactive proteins. In addition to proteins, human milk contains free amino acids (FAAs), which have not been well-studied. Of those, the FAAs glutamate and glutamine are by far the most abundant. Levels of these FAAs in human milk sharply increase during the first months of lactation, in contrast to most other FAAs. These unique dynamics are globally consistent, suggesting that their levels in human milk are tightly regulated throughout lactation and, consequently, that they might have specific roles in the developing neonate. Interestingly, free glutamine and glutamate are reported to exhibit immunomodulating capacities, indicating that these FAAs could contribute to neonatal immune development and to the unique protective effects of breastfeeding. This review describes the current understanding of the FAA composition in human milk. Moreover, it provides an overview of the effects of free glutamine and glutamate on immune parameters relevant for allergic sensitization and infections in early life. The data reviewed provide rationale to study the role of free glutamine and glutamate in human milk in the protection against neonatal allergies and infections.

Autism spectrum disorder (ASD) is a range of neurodevelopmental conditions that affect communication and social behavior. Besides social deficits, systemic inflammation, gastrointestinal immune-related problems, and changes in the gut microbiota composition are characteristic for people with ASD. Animal models showed that these characteristics can induce ASD-associated behavior, suggesting an intimate relationship between the microbiota, gut, immune system and the brain in ASD. Multiple factors can contribute to the development of ASD, but mutations leading to enhanced activation of the mammalian target of rapamycin (mTOR) are reported frequently. Hyperactivation of mTOR leads to deficits in the communication between neurons in the brain and to immune impairments. Hence, mTOR might be a critical factor linking the gut-brain-immune axis in ASD. Pharmacological inhibition of mTOR is shown to improve ASD-associated behavior and immune functions, however, the clinical use is limited due to severe side reactions. Interestingly, studies have shown that mTOR activation can also be modified by nutritional stimuli, in particular by amino acids. Moreover, specific amino acids are demonstrated to inhibit inflammation, improve gut barrier function and to modify the microbiota composition. In this review we will discuss the gut-brain-immune axis in ASD and explore the potential of amino acids as a treatment option for ASD, either via modification of mTOR activity, the immune system or the gut microbiota composition.

Background: Previously, maternal supplementation with short-chain galacto- and long-chain fructo-oligosaccharides (scGOS/lcFOS; ratio 9:1) was shown

Background: The maternal environment and early life exposure affect immune development in offspring.Objective: We investigated whether development of