M-Cells Contribute to the Entry of an Oral Vaccine but Are Not Essential for the Subsequent Induction of Protective Immunity against Francisella tularensis.
M-cells (microfold cells) are thought to be a primary conduit of intestinal antigen trafficking. Using an established neutralizing anti-RANKL (Receptor Activator of NF-κB Ligand) antibody treatment to transiently deplete M-cells in vivo, we sought to determine whether intestinal M-cells were required for the effective induction of protective immunity following oral vaccination with ΔiglB (a defined live attenuated Francisella novicida mutant). M-cell depleted, ΔiglB-vaccinated mice exhibited increased (but not significant) morbidity and mortality following a subsequent homotypic or heterotypic pulmonary F. tularensis challenge. No significant differences in splenic IFN-γ, IL-2, or IL-17 or serum antibody (IgG1, IgG2a, IgA) production were observed compared to non-depleted, ΔiglB-vaccinated animals suggesting complementary mechanisms for ΔiglB entry. Thus, we examined other possible routes of gastrointestinal antigen sampling following oral vaccination and found that ΔiglB co-localized to villus goblet cells and enterocytes. These results provide insight into the role of M-cells and complementary pathways in intestinal antigen trafficking that may be involved in the generation of optimal immunity following oral vaccination.
Department of Biology, South Texas Center for Emerging Infectious Disease, University of Texas at San Antonio, San Antonio, Texas, United States of America.|Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
Aimee L
AL
Cunningham
Department of Biology, South Texas Center for Emerging Infectious Disease, University of Texas at San Antonio, San Antonio, Texas, United States of America.
M Neal
MN
Guentzel
Department of Biology, South Texas Center for Emerging Infectious Disease, University of Texas at San Antonio, San Antonio, Texas, United States of America.
Jieh-Juen
JJ
Yu
Department of Biology, South Texas Center for Emerging Infectious Disease, University of Texas at San Antonio, San Antonio, Texas, United States of America.
Chiung-Yu
CY
Hung
Department of Biology, South Texas Center for Emerging Infectious Disease, University of Texas at San Antonio, San Antonio, Texas, United States of America.
Thomas G
TG
Forsthuber
Department of Biology, South Texas Center for Emerging Infectious Disease, University of Texas at San Antonio, San Antonio, Texas, United States of America.
Christopher S
CS
Navara
Department of Immunology, Juntendo University, Tokyo, Japan.
Hideo
H
Yagita
Department of Pathology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Ifor R
IR
Williams
Department of Biology, South Texas Center for Emerging Infectious Disease, University of Texas at San Antonio, San Antonio, Texas, United States of America.
Karl E
KE
Klose
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
Tonyia D
TD
Eaves-Pyles
Department of Biology, South Texas Center for Emerging Infectious Disease, University of Texas at San Antonio, San Antonio, Texas, United States of America.
Bernard P
BP
Arulanandam
D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D005260:Female; D005604:Francisella tularensis / Q000276:immunology*; D007109:Immunity; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D007422:Intestines / Q000166:cytology* / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D014406:Tularemia / Q000276:immunology* / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000276:immunology*
D001428:Bacterial Vaccines; D020381:Interleukin-17; D007376:Interleukin-2; D014613:Vaccines, Attenuated; D007371:Interferon-gamma