'Hygienic' lymphocytes convey increased cancer risk.
Risk of developing inflammation-associated cancers has increased in industrialized countries during the past 30 years. One possible explanation is societal hygiene practices with use of antibiotics and Caesarian births that provide too few early life exposures of beneficial microbes. Building upon a 'hygiene hypothesis' model whereby prior microbial exposures lead to beneficial changes in CD4+lymphocytes, here we use an adoptive cell transfer model and find that too few prior microbe exposures alternatively result in increased inflammation-associated cancer growth in susceptible recipient mice. Specifically, purified CD4+lymphocytes collected from 'restricted flora' donors increases multiplicity and features of malignancy in intestinal polyps of recipientApcMin/+mice, coincident with increased inflammatory cell infiltrates and instability of the intestinal microbiota. We conclude that while a competent immune system serves to maintain intestinal homeostasis and good health, under hygienic rearing conditions CD4+lymphocytes instead exacerbate inflammation-associated tumorigenesis, subsequently contributing to more frequent cancers in industrialized societies.
Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139.
Tatiana
T
Levkovich
Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 ; Laboratory of Pathology, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, Greece 54124.
Theofilos
T
Poutahidis
Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139.
Kelsey
K
Cappelle
Biological Engineering, Massachusetts Institute of Technology, Cambridge MA 02139 United States.
Mark B
MB
Smith
Biological Engineering, Massachusetts Institute of Technology, Cambridge MA 02139 United States.
Allison
A
Perrotta
Biological Engineering, Massachusetts Institute of Technology, Cambridge MA 02139 United States ; Broad Institute of MIT and Harvard, Cambridge, MA, United States.
Eric J
EJ
Alm
Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139.
Susan E
SE
Erdman
ApcMin/+; cancer; hygiene; inflammation; microbiome