Granzyme A (GZMA) is a serine protease secreted by cytotoxic lymphocytes, with Gzma -/- mouse studies having informed our understanding of GZMA’s physiological function. These data do not support a contention that TLR9 is required for GZMA’s bioactivity. Tlr9 -/- mice did not show an increased viremia ( f). After CHIKV infection, foot swelling was again increased in Tlr9 -/- ( d), but not Tlr9 M7Btlr/Mmjax mice ( e). 2000), with 129/SvJ mice showing increased inflammatory infiltrates in certain settings (Hoover-Plow et al., 2008). ![]() Tlr9 -/- mice also have the Nnt deletion ( c) however, they are on a mixed 129/Ola and C57BL/6 background (Hemmi et al. After GZMA injection, Tlr9 -/- mice showed increased foot swelling ( a), whereas C57BL/6J- Tlr9 M7Btlr/Mmjax mice showed no significant difference ( b). ( e) Female C57BL/6J- Tlr9 M7Btlr/Mmjax mice (n = 6 mice and 12 feet per group) were infected as for ( d). ( d) Female 8–10-week-old Tlr9 -/- and 6J mice (n = 6 mice and 12 feet per group) were infected with chikungunya virus (CHIKV) and feet measured over time. ( c) Tlr9 -/- mice (like 6J) do not encode the full Nnt gene. Tlr9 M7Btlr/Mmjax mice have a Tlr9 missense point mutation and do not respond to oligonucleotides containing CpG motifs ( ). ( b) As for ( a) using Tlr9 M7Btlr/Mmjax and 6J mice. Tlr9 -/- mice were derived from 129/Ola × C57BL/6F1 progeny ( ). ![]() ( a) Tlr9 -/- and 6J mice were injected intraplantar into the feet with 5 µg recombinant mouse granzyme A (GZMA) in 20 µl and foot swelling measured over time as described ( Schanoski et al., 2019) (n = 4 mice and four feet per group statistics by Kolmogorov–Smirnov tests). Supplementary file 8: No evidence for TLR9 involvement.
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