Titans quarterback Jake Locker left in the first quarter and did not return after hurting his left, non-throwing shoulder on a hit by Glover Quin. Locker hurt the same shoulder in the season opener against New England.
Tennessee coach Mike Munchak said Locker was "sore" and would undergo an MRI exam Monday.
Matt Hasselbeck threw two touchdown passes in relief of Locker for the Titans. Chris Johnson carried 25 times for 141 yards, more than tripling his rushing total through the first three games.
The Texans led 14-7 at halftime, but the offense bogged down for a while after that. Leave it to the defense to get Houston going again.
Hasselbeck threw behind tight end Taylor Thompson and the ball ricocheted to Manning, who weaved his way 55 yards for a touchdown with 9:21 left in the third quarter. Manning signed with Houston as a free agent in 2011 and helped transform a defense that ranked last against the pass the previous season.
Manning's play not only re-ignited the restless fans at Reliant Stadium, it also seemed to wake up the offense.
The Texans went without a huddle and breezed down the field in just over two minutes. Foster broke a 16-yard run and Schaub threw a 28-yard touchdown pass to tight end Owen Daniels.
Down 28-7, the Titans were forced to throw more despite Johnson's best game of the season.
Jackson, a cornerback, knocked away a deep pass to Kendall Wright, and Watt sacked Hasselbeck again near the end of the third quarter.
Hasselbeck fumbled when he was hit by Antonio Smith in the fourth quarter, and Watt recovered at the Tennessee 24. Shayne Graham kicked a 33-yard field goal with 5:38 left.
Tennessee crossed midfield and Jackson intercepted Hasselbeck and raced untouched to the end zone, high-stepping the last 10 yards.
Hasselbeck threw a short TD pass to Wright in the final minute. He finished 17 of 25 for 193 yards.
The Texans led 7-0 when Locker was hurt on the Titans' second series. On third down, Quin blitzed and plowed into Locker for his first career sack. Locker immediately grabbed his left hand and arm as he lied on the turf. He eventually walked to the locker room on his own, and later returned in street clothes, his left arm in a sling.
Houston took over near midfield, converted a fourth-and-1 from the Tennessee 38 and Foster scored on a 4-yard run.
Hasselbeck, seeing his first action since the opener, threw a 25-yard pass to tight end Jared Cook. The Texans smothered Johnson for a 6-yard loss to force another punt for Tennessee.
Johnson later broke a 19-yard run and the Titans' offense showed some life with Hasselbeck taking the snaps. Hasselbeck found fullback Craig Stevens for a 19-yard touchdown with 7:52 left in the first half.
Johnson limped off the field late in the first half, after he was tackled by Texans linebackers Brian Cushing and Connor Barwin. He returned for the Titans' first series of the third quarter.
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