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Maternal milk ILCs and adaptive immune cells populate neonatal organs

Cellular & Molecular Immunology volume 17, pages 665–667 (2020)Cite this article

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How does the neonatal immune system decide which of the millions and millions of microbes it encounters during and soon after birth are commensal and which are pathological? This is not a trivial issue. Excessively vigorous responses to commensal bacteria cause unnecessary collateral tissue damage and loss of the potentially beneficial microbial flora needed for host metabolism. On the other hand, insufficient immune defense against invading, harmful, microbes is also very problematic, if not lethal.1 While the mechanisms for self-tolerance have been the subject of extensive investigations since the mid-1950s, such is not the case for selective unresponsiveness to commensal microbial flora residing on the skin or the mucosa of the gastrointestinal track.2

The initial interactions between the immune system, the gut microbiome, and the gastrointestinal tract are complex and critical, and excessive inflammatory reactions are a primary contributor to the development of necrotizing enterocolitis.3 Compounding the problem is the well-established observation that neonates have immature innate and adaptive immunity, both qualitatively and quantitatively.4 Importantly, while most of the neonatal innate immune cells (e.g., neutrophils and monocytes) present have blunted activity and decreased frequencies compared to their adult counterparts, innate lymphoid cells (ILCs), a distinct cellular component of innate immunity, show a higher level of activity and are more present during the period of infancy than their counterparts in later stages of life and adulthood, which may suggest a role for ILCs in the variable susceptibility to certain conditions over the life time.5 ILCs are immune effector cells that are capable of a broad spectrum of functions and interactions with other groups of host cells. Due to their appearance at early stages of ontogeny and their evolution throughout embryonic development, ILCs can affect and may be influenced by host cellular, molecular, and environmental factors, conferring the host a viable and robust source of plastic immune cells with the capacity to adapt and contribute to the immune system from the neonatal phase to the old age.1 Furthermore, neonatal neutrophils have many deficiencies compared to their adult counterparts, ranging from a decreased presence in the bone marrow, decreased surface markers, and decreased chemotaxis to hydrogen peroxide production and limited ability to kill pathogens.6 Neonatal macrophages are also different from adult macrophages in many ways, including having a defective response to and defective production of inflammatory cytokines, lower levels of CCL3, CCR1, and CCR5, and an aberrant response to bacterial endotoxin, among other features.7 With all these competing demands and internal constraints, maternal transfer of cells and soluble factors represents a promising solution. Data from nursing humans and mice strongly support a maternal influence.8 In this report, we used a murine litter swab model to test the novel hypothesis that maternal immune cells can survive the passage through the neonatal gastrointestinal tract and populate the parenchyma of various organs despite MHC mismatch.

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Fig. 1: The presence and distribution of ILCs and other leukocytes in various tissues.

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Authors and Affiliations

  1. Children’s Hospital of Georgia and Medical College of Georgia, Augusta University, Augusta, GA, USA

    Jack C. Yu

  2. Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta University, Augusta, GA, USA

    Hesam Khodadadi, Évila da Silva Lopes Salles & Babak Baban

  3. Department of Surgery, Medical College of Georgia, Augusta University, Augusta, GA, USA

    Fairouz Chibane

  4. Division of Neonatology, Department of Pediatric, Medical College of Georgia, Augusta University, Augusta, GA, USA

    Jatinder Bhatia

Authors
  1. Jack C. Yu
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Contributions

J.C.Y.: Study conception and design, analysis and interpretation of data, and drafting the article. H.K.: Acquisition of data and drafting the article. F.C.: Writing and editing the article. J.B.: Data interpretation and editing. B.B.: Study conception and design, acquisition, analysis, and interpretation of data, and drafting the article.

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Correspondence to Jack C. Yu or Babak Baban.

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The authors declare no competing interests.

Disclosure

This study was partly supported by institutional funds (provided to B.B.) and partly supported by the Milford B. Hatcher Endowment (provided to J.Y.). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Declaration

All studies and procedures followed the Public Health Service Guide for the Care and Use of Laboratory. Animals and Augusta University guidelines.

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Yu, J.C., Khodadadi, H., Lopes Salles, É.d.S. et al. Maternal milk ILCs and adaptive immune cells populate neonatal organs. Cell Mol Immunol 17, 665–667 (2020). https://doi.org/10.1038/s41423-019-0350-x

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