CCR9+ T cells contribute to the resolution of the inflammatory response in a mouse model of intestinal amoebiasis.
Analysis of the mechanisms underlying the inflammatory response in amoebiasis is important to understand the immunopathology of the disease. Mucosal associated effector and regulatory T cells may play a role in regulating the inflammatory immune response associated to Entamoeba histolytica infection in the colon. A subpopulation of regulatory T cells has recently been identified and is characterized by the expression of the chemokine receptor CCR9. In this report, we used CCR9 deficient (CCR9(-/-)) mice to investigate the role of the CCR9(+) T cells in a murine model of E. histolytica intestinal infection. Intracecal infection of CCR9(+/+), CCR9(+/-) and CCR9(-/-) mice with E. histolytica trophozoites, revealed striking differences in the development and nature of the intestinal inflammatory response observed between these strains. While CCR9(+/+) and CCR9(+/-) mice were resistant to the infection and resolved the pathogen-induced inflammatory response, CCR9(-/-) mice developed a chronic inflammatory response, which was associated with over-expression of the cytokines IFN-γ, TNF-α, IL-4, IL-6 and IL-17, while IL-10 was not present. In addition, increased levels of CCL11, CCL20 and CCL28 chemokines were detected by qRT-PCR in CCR9(-/-) mice. E. histolytica trophozoites were identified in the lumen of the cecum of CCR9(-/-) mice at seven days post infection (pi), whereas in CCR9(+/+) mice trophozoites disappeared by day 1 pi. Interestingly, the inflammation observed in CCR9(-/-) mice, was associated with a delayed recruitment of CD4(+)CD25(+)FoxP3(+) T cells to the cecal epithelium and lamina propria, suggesting that this population may play a role in the early regulation of the inflammatory response against E. histolytica, likely through IL-10 production. In support of these data, CCR9(+) T cells were also identified in colon tissue sections obtained from patients with amoebic colitis. Our data suggest that a population of CCR9(+)CD4(+)CD25(+)FoxP3(+) T cells may participate in the control and resolution of the inflammatory immune response to E. histolytica infection.
CBRL, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico.
A E
AE
Rojas-López
G
G
Soldevila
S
S
Meza-Pérez
G
G
Dupont
P
P
Ostoa-Saloma
M A
MA
Wurbel
J
J
Ventura-Juárez
L
L
Flores-Romo
E A
EA
García-Zepeda
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D054413:Chemokine CCL11 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054418:Chemokine CCL20 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004404:Dysentery, Amebic / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D004748:Entamoeba histolytica / Q000276:immunology* / Q000502:physiology; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054388:Receptors, CCR / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053058:Trophozoites / Q000276:immunology / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
C119309:CC chemokine receptor 9; C511142:Ccl28 protein, mouse; D054413:Chemokine CCL11; D054418:Chemokine CCL20; D019742:Chemokines, CC; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018836:Inflammation Mediators; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6; D054388:Receptors, CCR; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma