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It feels like only yesterday England came painfully close to being crowned Euro 2020 champions on home soil, only for them to be defeated on penalties by the very opponent they face on Thursday night.
But despite entering the qualifiers off the back of a quarter-final knockout at the World Cup, England manager Southgate believes it's actually the perfect time for his side to face their former foes.
"You want a big challenge immediately," he told talkSPORT's England correspondent Faye Carruthers on the eve of the game.
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"We had that after the Euros, going to Hungary, going to Budapest which was bouncing and we gave one of our best performances I think since I've been manager.
"Tomorrow is a similar sort of challenge - a high level opponent, somewhere we haven't won for too many years that we want to mention and that's a great test for us.
"I think it's the perfect start to the qualification. Of course, if you could hand pick your group you probably wouldn't have England Italy as one of your fixtures.
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"But it is what it is and to play them now is as good a time as any."
England didn't face Italy at Qatar 2022 after the European champions failed to qualify for the competition.
But the countries have met since that dramatic Euro final at Wembley Stadium, playing against each other twice in England's horror Nations League campaign last year with the outcome being one 0-0 draw and one 1-0 win for Italy.
One England star that featured in the second fixture was Manchester City forward Phil Foden, who also started in England's final three games in Qatar after missing out on the first XI in the opening matches.
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But despite Foden being able to be deployed on the wing and in midfield, Southgate has hinted he'll continue to use the Man City star in the position he has the most experience in should get in his XI.
"With Phil, he has got versatility, but you have to look where his club play him," the Three Lions manager said, "That's wide on the left or wide on the right.
"Against lesser opponents he plays as a no.10 or in midfield, so [Man City] are still looking at his evolution as to what he might be but in the big games he plays from the side and that's where most of his experiences are."
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Meanwhile, Brentford striker Ivan Toney, who was also called up for the Nations League last year - was given a call-up for this month's two England fixtures, too.
Despite not being taken to Qatar with Newcastle's Callum Wilson preferred instead, the Bees star now has the third best scoring record in the Premier League this season, leading Southgate to give him another chance to earn his first England cap.
When asked how he's fitting into the England camp, Southgate said: "Very good. He'll feel more settled in the group coming back for the second time.
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"I've liked his performances with his club, he's definitely in good form. He's definitely not looked out of place in the training sessions but that was the same the last time he was with us [for the Nations League].
"We're happy with what he's done."