Table 1.

Perturbations of type I IFN signaling in mouse models and consequences for infection with bacteria of the Mycobacterium tuberculosis complex.

Mouse strain/Mtb susceptible (S) or resistant (R)	Type I IFN perturbation	Mycobacteria	Type I IFN response	Bacterial burden	Pathology	Survival	Reference
C57BL/6 (R)	Ifnar1−/−	H37Rv	Reduced IFN-β in lung homogenate 18 and 25 days p.i.	Comparable to WT on days 18 and 25 p.i.	n.d.	No mortality in WT and Ifnar1−/− (day 70 p.i.)	(94)
	Ifnar1−/−	BTB 02-171	n.d.	Comparable to WT on days 24 and 27 p.i.	Comparable to WT at day 27 p.i.	No mortality in WT and Ifnar1−/− (day 50 p.i.)	(73)
	Ifnar1−/−	Erdman	n.d.	Comparable to WT on days 1, 10, and 21 p.i. in the lungs. Reduced bacterial burden in spleen on days 10 and 21 p.i.	n.d.	n.d.	(33)
	Ifnar1−/−	Mycobacterium africanum GM041182	n.d.	Reduced bacterial burden in lungs on day 292 p.i. in Ifnar1−/− mice	Pathology diminished in Ifnar1−/− compared to WT mice	Ifnar1−/− mice survived 292 days p.i., small number of WT mice succumbed >200 days p.i.	(95)
	Poly-ICLC (i.n.) twice weekly for 28 days, starting (a) 1 day or (b) 4 months post infection	H37Rv	(b) Poly-ICLC increased Ifnb and Ifna expression in lungs of WT mice; levels equivalent between poly-ICLC and poly-ICLC+Mtb	(a) and (b) increased bacterial burden in lungs. Was prevented in Ifnar−/− mice	(a) and (b) increased lung pathology	(b) reduced survival	(97)
	Intranasal influenza A virus (a) 28 days before or (b) 1 and 14 days (2 different IVA subtypes) after Mtb infection	H37Rv	n.d.	Slightly elevated lung bacterial burden (a) 120 days (b) 27 days post Mtb infection	(a) increased lung inflammation on day 120 post Mtb infection	(a) impaired survival of mice >160 days	(96)
				(a) No effect on lung Mtb burden on days 28/31 and 63 post Mtb infection
B6D2/F1 (R)	Purified mouse IFNα/β (5 days/weeks for 4 weeks) post infection	HN878	n.d.	Higher bacterial burden in lungs at day 28 for HN878 + IFNα/β compared to HN878 only mice	n.d.	IFNα/β administration significantly impaired survival	(89)
	Anti-IFNα/β (A1AB/5; i.p. every 48 h for 4 weeks starting 24 h prior to Mtb)	HN878	Lung IFN-α mRNA at d28 p.i. slightly elevated for anti-IFNα/β treated mice	Equal bacterial burden in lungs	n.d.	Enhanced survival of anti-IFNα/β treated mice	(90)
129 (S)	Ifnar1−/−	H37Rv	n.d.	Slightly decreased lung bacterial burden in Ifnar1−/− mice 21 days p.i.	Diminished pathology in Ifnar1−/− mice in Ifnar1−/− mice 21 days p.i.	Most WT mice died within 40 days p.i., all Ifnar1−/− mice survived (d70)	(91)
	Ifnar1−/−	HN878 CDC1551	n.d.	n.d.	n.d.	Small survival benefit for Ifnar−/− infected with HN878; Ifnar−/− survived significantly longer with CDC1551 infection compared to HN878	(90)
	Ifnar1−/−	H37Rv HN878 CSU123 CDC1551 Erdman-KO1	n.d.	Reduced bacterial burden in lungs of Ifnar1−/− mice compared to WT mice (>25 days p.i.) for all Mtb strains	Increased lung pathology in WT mice infected with HN878 compared to H37Rv, CDC1551 or Erdman-KO1	Equivalent survival of Ifnar1−/− (129 background) and C57BL/6 WT mice during infection with HN878, CDC1551, and Erdman-KO1	(93)
C57BL/6/129 (S)	Ifnar1−/−	Erdman	n.d.	Slightly increased lung bacterial burden at 10, 20, and 40 days p.i. compared to WT	n.d.	n.d.	(101)
				Comparable bacterial burden at 80 days p.i.
Il-1r−/− on C57BL/6 (S)	Ifnar1−/−	H37Rv	n.d.	n.d.	n.d.	Il-1r/Ifnar1−/− partially rescued survival of highly susceptible Il1r1−/− mice but still impaired compared to WT and Ifnar1−/−; no difference between WT and Ifnar1−/− until day 80 p.i.	(92)
Ifngr1−/− on C57BL/6 (S)	Ifnαr1−/−	H37Rv	Slightly elevated IFN-β protein in lung homogenate of Ifngr/Ifnar1−/− compared to Ifngr−/− mice 25 days p.i.	Comparable bacterial burden in lung and MLN in Ifngr/Ifnar1−/− and Ifngr−/−; both higher than WT and Ifnar1−/− 25 days p.i., no difference between WT and Ifnar1−/−	Severe pathology in Ifngr−/− even more exacerbated in Ifngr/Ifnar1−/−, both higher than WT	Ifngr/Ifnar1−/− succumbed approx. 7 days earlier than Ifngr−/−	(94)
	Ifnar1−/−	BTB 02-171	n.d.	Lung bacterial burden in Ifngr/Ifnar1−/− mice increased compared to Ifngr−/−; both higher than WT and Ifnar1−/− 24 and 27 days p.i., no difference between WT and Ifnar1−/−	Severe pathology in Ifngr−/− even more exacerbated in Ifngr/Ifnar1−/−, both higher than WT and Ifnar1−/−	Ifngr/Ifnar1−/− succumbed approx. 3 days earlier than Ifngr−/−; no mortality in WT and Ifnar1−/− (until day 50 p.i.)	(73)

Ifnar1, interferon alpha receptor 1; Ifngr, interferon gamma receptor; Il-1r, interleukin 1 receptor; WT, wild-type; Mtb, M. tuberculosis; IFN, interferon; p.i., postinfection; i.n., intranasal; n.d., not determined; Poly-ICLC, polyinosinic-polycytidilic acid and poly-l-lysine double stranded RNA.