It's Week 6 and the leaders of the AFC East will meet the leaders of the AFC South in Nashville for a primetime game on Monday night.

It will be Buffalo's second-straight primetime matchup and the fourth time these two will meet in the last four seasons. Here are some storylines to follow as we move closer to Monday.

1. Bills face Tennessee for the fourth time in four seasons

The Bills have two wins and a loss against the Titans in their last three meetings. Last year's game against Tennessee was rescheduled due to a COVID-19 outbreak among the coaching staff and players. It was originally scheduled for Sunday night but had to be moved to Tuesday due to the outbreak. Buffalo lost in that Week 5 matchup 42-16.

It was a frustrating game to watch because Buffalo was 4-0 coming into the contest and made some uncharacteristic errors. Bills quarterback Josh Allen finished 26-41 (63.4%) for 263 passing yards, throwing for two touchdowns and two interceptions. Buffalo's defense limited Titans running back Derrick Henry to only 57 rushing yards but allowed touchdowns on every one of Tennessee's six red zone opportunities.

Titans head coach Mike Vrabel said he doesn't think last year's win will help them prepare for Monday night's game.

"I would doubt it," Vrabel said. "They're scoring it well, moving the ball. It looks like the quarterback looks like a running back with an elite arm. It looks like it's a Wildcat that throws for 350 yards a game."

In 2019, the Bills beat the Titans 14-7. Allen was 23-32 (72%) for 219 passing yards, throwing for two touchdowns and one interception. Wide receiver John Brown was the leading receiver with five receptions for 75 yards and tight end Lee Smith caught an eight-yard touchdown pass from Allen.

Buffalo's defense limited Tennessee to just 252 total yards, including 102 rushing yards. Henry recorded 78 rushing yards and one rushing touchdown off 20 attempts. The Titans missed four field goals and converted only four of their 14 third down opportunities.

In 2018, Buffalo beat Tennessee by one point with a final score of 13-12. Allen was 10 of 19 (52.6%) for 82 yards, throwing one interception. Both teams combined for just 444 total yards and Buffalo's defense held Henry to 56 rushing yards. Running back LeSean McCoy was Buffalo's leading rusher and receiver, totaling 24 attempts for 85 yards on the ground and two receptions for 23 yards. The two teams combined for six field goals and Allen had the lone touchdown of the game.

Both teams look quite different from their 2018 matchup but two important players in Allen and Henry have remained the same. It'll be a task for each team to try to shut down the player that provides the fire power on each offense.

2. Taking down Derrick Henry

Buffalo's defense has faced Titans running back Derrick Henry three times in the last three seasons. Henry has totaled 50 carries for 191 rushing yards (3.82 yards per carry) and three touchdowns in those matchups.

The Bills have held Henry to under 60 rushing yards in two of those three games. Henry has been held under 60 rushing yards just 17 times in the 52 games he has started. But that doesn't mean the task to take down Henry is any easier just because the Bills have limited his impact in the past.

Henry leads the league with 640 rushing yards, seven rushing touchdowns and 34 rushing first downs. He recorded 29 carries for 130 rushing yards and three touchdowns last week against the Jaguars. The return of defensive tackle Star Lotulelei gives the Bills an added defender who can help stop the run and Buffalo also has the third-best run defense allowing only 78.4 rushing yards per game. But defensive coordinator Leslie Frazier knows they will have to come up with a good game plan and execute it at the highest level in order to have success in slowing down Henry.

"He's a really, really good back and we're going to have our hands full trying to contain him," Frazier explained. "Completely different style of offense that's centered around their running back as opposed to their receivers and quarterback, so it will be a challenge. And as we get into it and learn a little bit more about what they're doing currently on offense, we'll try to come up with some ways to slow him down."

3. How Buffalo's defense stacks up against Tennessee

Through five games, the Bills have the best defense in the NFL. They're at the top of the pack allowing just 12.8 points per game and 251.8 total yards per game. So how does Buffalo's defense compare to Tennessee's offense?

Tennessee's strength is its run game, which ranks third averaging more than 165 rushing yards per game. Buffalo has been good at shutting teams down when they try to run the football allowing an average of under 80 rushing yards per game.

Titans quarterback Ryan Tannehill has been sacked 20 times this season, which is more than any quarterback. Buffalo's defense has sacked quarterbacks 14 times, which ties for fifth in the league.

In addition to having the 10th best offense averaging 389.2 total yards per game and averaging 26.4 points per game, Tennessee ranks third averaging 25.4 first downs per game. Buffalo's defense has limited opponents first downs by allowing an average of 15.4 per game.

The Titans have been toward the bottom of the league when it comes to converting third downs and their red zone efficiency. Their touchdown percentage in the red zone is 56.5% (26th) and convert third down opportunities 38.6% of the time (20th). Buffalo's defense limits teams to a 35.7% red zone efficiency (tied for 1st) and holds opponents to an average of 32.3% third down conversion percentage (5th).

Tennessee hasn't excelled in the passing game and is averaging 221.4 passing yards per game (26th). Tannehill has also thrown for only six passing touchdowns in five games. Buffalo's defense is allowing only 173.4 passing yards per game (2nd) and has nine interceptions (ties for 2nd) through the first five weeks.

4. Another primetime opportunity for Josh Allen and his offense

Bills quarterback Josh Allen will get his second primetime opportunity of the season this week. Allen had impressive performance against the Chiefs on the Sunday Night Football stage. The quarterback threw for 315 yards, recorded four total touchdowns and a passer rating of 139.1. Allen was 6 of 6 on completions of at least 20 yards, two of which were touchdowns.

Sunday's game wasn't Allen's first standout performance under the lights. The QB excels on the stage. Since coming into the league, Allen has won five of six primetime matchups. In those games, he has thrown for 16 touchdowns and averages a passer rating of 106.2.

"I know Josh is a tireless worker, he works to improve and obviously he's improved every year that he's been here and that's what you hope for any player," Bills offensive coordinator Brian Daboll said. "But he's a special kind of guy when you talk about commitment and dedication to a craft, leadership with your teammates and laying it on the line."

Allen is quarterbacking an offense that's the best in the league averaging 34.4 points per game. Their +108 point differential is the highest in the NFL and the sixth-highest in NFL through five games since 1970.

5. Becoming the hunted

Buffalo has won four straight games and is viewed as the best and most complete team in the NFL by many league analysts. That doesn't mean the Bills will sway from their established identity as the team prepares for its next opponent.

The Bills know what it feels like to be the hunter, going after teams and trying to knock them off during their climb to becoming a perennial playoff team. Many believe the Bills no longer qualify as the hunter after making it to the AFC Championship game in 2020 and have turned into the team that others are trying to beat and trying to become.

Within the walls of One Bills Drive, the Bills still operate with a chip on their shoulders knowing they haven't accomplished all their goals yet.

"Until you win it, in my mind, we're still hunting," Bills general manager Brandon Beane said before the season started. "Will people be hunting us? Yes, starting with our division. But again, I think our guys understand that what we did last year doesn't mean anything and let's hit the reset button. Our guys play with a chip, I think it starts with Sean.

"He does a great job. He coaches with a chip, he walks around the halls with a chip and our guys feel that."

And they'll prepare for this week's matchup with that same chip on their shoulder knowing there's 12 games left in the regular season.

"That's always a challenge with all the noise that comes from you guys outside the building from time to time," McDermott said. "But it takes leadership, not talking about coach leadership, I'm talking about player-driven leadership. We've got good leadership in our locker room and I'm counting on those guys this week."