Maternal Immunization Confers Protection to the Offspring against an Attaching and Effacing Pathogen through Delivery of IgG in Breast Milk

• Published in: Cell host & microbe Vol. 25; no. 2; pp. 313 - 323.e4
• Main Authors: Caballero-Flores, Gustavo, Sakamoto, Kei, Zeng, Melody Y., Wang, Yaqiu, Hakim, Jill, Matus-Acuña, Violeta, Inohara, Naohiro, Núñez, Gabriel
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.02.2019
• Subjects: Animals; Animals, Newborn; Antibodies, Bacterial - immunology; Antigens, Bacterial - immunology; breast milk; C. rodentium; Citrobacter rodentium; Citrobacter rodentium - immunology; Disease Models, Animal; enteric infection; Enterobacteriaceae Infections - prevention & control; EPEC; IgG; Immunization, Passive; Immunoglobulin G - immunology; Immunologic Factors - immunology; LEE-virulence factors; maternal vaccination; Mice; Milk - immunology; mucosal immunity; neonatal immunity; Survival Analysis; maternal vaccination; LEE-virulence factors; enteric infection; IgG; EPEC; breast milk; Citrobacter rodentium; C. rodentium; neonatal immunity; mucosal immunity
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2018.12.015

Owing to immature immune systems and impaired colonization resistance mediated by the microbiota, infants are more susceptible to enteric infections. Maternal antibodies can provide immunity, with maternal vaccination offering a protective strategy. We find that oral infection of adult females with the enteric pathogen Citrobacter rodentium protects dams and offspring against oral challenge. Parenteral immunization of dams with heat-inactivated C. rodentium reduces pathogen loads and mortality in offspring but not mothers. IgG, but not IgA or IgM, transferred through breast milk to the intestinal lumen of suckling offspring, coats the pathogen and reduces intestinal colonization. Protective IgG largely recognizes virulence factors encoded within the locus of enterocyte effacement (LEE) pathogenicity island, including the adhesin Intimin and T3SS filament EspA, which are major antigens conferring protection. Thus, pathogen-specific IgG in breast milk induced during maternal infection or immunization protects neonates against infection with an attaching and effacing pathogen. [Display omitted] •Maternal immunization confers protection to offspring against C. rodentium infection•Maternal IgG in breast milk, but not IgA or IgM, is required for neonatal protection•Maternal IgG coats the pathogen and increases its engulfment by neutrophils•LEE-specific antibodies are required to confer protection in the offspring Caballero-Flores et al. demonstrate that maternal immunization with heat-inactivated C. rodentium or surface pathogen antigens protects neonatal mice against pathogen oral challenge. Protection was mediated by the delivery of pathogen-specific IgG through breast milk, which coated the pathogen, increased its phagocytosis, and decreased epithelial attachment in the gut.