Partial depletion of CD4+CD25+Foxp3+ T regulatory cells significantly increases morbidity during acute phase Toxoplasma gondii infection in resistant BALB/c mice

Abstract

CD4 þ CD25 þ Foxp3 þ T regulatory (Treg) cells, are known to regulate responses to infectious agents. Here we compared disease progression in BALB/c and C57BL/6(B6) mice infected perorally with Toxoplasma gondii for 7 days and examined the affect of partial depletion of Treg cells in these mice. BALB/c mice were seen to be resistant to peroral infection whereas B6 mice were susceptible in terms of mortality. Although the depletion of Treg cells before infection had no effect on the survival of B6 or BALB/c mice, it resulted in increased parasite burdens in BALB/c mice, especially in the lamina propria, but not in B6 mice. Pro-inflammatory cytokines were also increased in Treg cells depleted BALB/c mice as compared to B6 mice. In addition Treg cell depleted BALB/c mice displayed increased ileal histopathology compared to their non-treated counterparts. These findings provide evidence for the contribution of Treg cells, in the resistance of BALB/c mice against peroral T. gondii infection.

Role of CD4+Foxp3+Regulatory T Cells in Protection Induced by a Live Attenuated, Replicating Type I Vaccine Strain of Toxoplasma gondii

“…This low IL-2 level may therefore be correlated with the higher level of expression of CD25 by Foxp3 ϩ cells. This reduced IL-2 level in cells from animals infected with T. gondii has been described by others (14,19,24). A reduced number of Tregs during the acute phase of T. gondii infection is a consequence of a reduced IL-2 availability (14,19).…”

“…This reduced IL-2 level in cells from animals infected with T. gondii has been described by others (14,19,24). A reduced number of Tregs during the acute phase of T. gondii infection is a consequence of a reduced IL-2 availability (14,19). IL-2 is also involved in the transient immunosuppression observed during acute toxoplasmosis (24,25).…”

“…In resistant BALB/c mice, Tregs are thought to reduce immunopathology since depletion of these cells induces morbidity due to the increased production of proinflammatory cytokines and higher parasite burden after oral infection (19). In this study, mice of both the resistant BALB/c and susceptible C57BL/6 strains had higher CD4 ϩ Foxp3 ϩ counts at the local level at 6 days postinfection than naive mice, and the absolute count in the resistant strain was higher than that in the susceptible strain.…”

“…The collapse of Tregs is correlated with pathogenicity and occurs only under highly pathogenic conditions since oral infection of BALB/c mice with a type II strain did not induce a reduction in the levels of Tregs (14). However, depletion of Tregs in these mice resulted in morbidity associated with a high parasite burden and increased ileal pathology compared to that in control BALB/c mice (19), suggesting a role of Tregs in protection during acute infection.…”

“…They constitutively express the interleukin-2 (IL-2) receptor alpha chain (IL2R␣), a surface receptor also known as CD25, and the intracellular fork head box-p3 transcription factor (Foxp-3) marker (16). The role of Tregs after infection with type II strains has been fully described (14,(17)(18)(19)(20)(21), and Tregs have been clearly implicated in the mortality of C57BL/6 mice after oral infection in the lethal ileitis model (14). The collapse of Tregs is correlated with pathogenicity and occurs only under highly pathogenic conditions since oral infection of BALB/c mice with a type II strain did not induce a reduction in the levels of Tregs (14).…”