Legionella pneumophila is an opportunistic human pathogen and the major cause of an acute pneumonia known as Legionnaire’s Disease. Upon inhalation, the bacteria replicate in alveolar macrophages (AM), within an intracellular vacuole termed the Legionella containing vacuoles (LCVs). Till now, little is known about how phagocytes control L. pneumophila lung infection. Recently, we found that monocyte-derived cells (MCs) are rapidly recruited into the lungs of L. pneumophila infected mice and that optimal clearance of the bacteria by MC, but not AMs and neutrophils, required interferon γ (IFNγ). To understand the mechanisms of MC restriction, the transcriptome of MCs obtained from L. pneumophila infected wildtype and ifnγ-/- mice was compared by RNA-sequencing. Gene ontology analysis showed enrichment of interferon-stimulated GTPases (ISGases) in MCs of wildtype mice compared to ifnγ-/- mice. Here, we found that Gbp1 and Irga6 overexpression contributes to the restriction of L. pneumophila replication in IFNγ-dependent manner in immortalized bone marrow derived macrophages (iBMDMs). While IFNγ is observed to disrupt effector protein translocation of Dot/Icm secretion system of L. pneumophila in iBMDMs, ISGases seem to have no effect on the effector protein translocation. Further, we found Gbp1 and Irga6 contribute to LCV rupture and autophagy to clean L. pneumophila by promoting the colocalization of Galectin-3 and Lamp1 with L. pneumophila in IFNγ activated iBMDMs. In addition, we found that IFNGR1 expression is significantly downregulated in AMs and neutrophils, but not MCs, during L. pneumophila lung infection. We confirmed downregulation of IFNGR1 in iBMDMs and showed that the downregulation relied on both MyD88 and Trif mediated NF-κB activation and was independent of type I IFN signalling, Irf3/7, Ripk3 and Bcl6 in macrophages. We propose that the reason AMs are unable to effectively restrict L. pneumophila replication in vivo is in part due to downregulation of IFNGR1.