[69]AgeCourse of the infection in old vs. young mice-Bacterial burden in lungs and spleen
-mRNA from lung tissue-No differences in bacterial burden between young and old mice
-More bacterial dissemination in old mice
-Reduced lymphocyte and cytokine mRNA copies in old mice[70,71]AgeCourse of the infection compared between mice of different ages-Bacterial burden in lungs
-Accumulation of lymphocytes in lungs and spleens
-Cytokine production by lymphocytes-Incremented presence of CD4 and CD8 T cells in the organs of old mice
-Increased production of Th1 cytokines by T cells of old mice
-Reduced bacterial burden in old mice[72,73,74]AgeCourse of the infection compared between mice of different ages-Survival of infected animals
-Bacterial burden in lungs, spleen and liver
-Lymphocyte’s isolation and characterization
-Characterization of alveolar lining fluid (ALF) of old mice
-AM’s isolation and characterization upon M. tuberculosis infection-Reduced survival of old animals [72]; no effect on survival [73]
-Inability of old mice to clear the infection from the organs
-Lack of T cell response in old mice
-ALF from old mice promotes the development of tuberculosis
-AMs populations from old mice promote the development of tuberculosis[95,96]SexCourse of the infection in males vs.
females-Survival of infected animals
-Bacterial burden in lungs, spleen and lymph nodes
-Histological analysis of damaged lungs
-Pro-inflammatory cytokine production
-Lymphoid aggregates formation-Reduced survival of males
-Higher bacillary loads in males
-Same pulmonary damaged area between sexes.
-Inflammatory cytokines production more elevated in males
-Smaller lymphoid aggregates in males[97,98]SexSteroid effects upon the course of the infection *-Survival of infected animals
-Bacterial burden in lungs and spleen-Reduced survival of the animals that received cortisone or corticotrophin
-High bacillary loads in animals that received cortisone or corticotrophin[99]SexSteroid effects upon the course of the infection *-Survival of infected animals
-Bacterial burden in lungs and spleen
-Cytokine profile expression
-Histological analysis of damaged lungs-Reduced survival in mice with high levels of testosterone
-High bacillary load in mice with high levels of testosterone
-Reduced expression of pro-inflammatory cytokines in mice with high levels of testosterone
-Bigger damaged area in mice with high levels of testosterone[100]SexSteroid effects upon the course of the infection *-Survival of infected animals
-Bacterial burden in lungs
-Histological analysis of damaged lungs
-Presence of delayed hypersensitivity (DH)
-Cytokine profile expression-Enhanced survival in mice treated with steroids
-Lower bacillary loads in mice treated with steroids
-Smaller pulmonary damage in mice treated with steroids
-More sustained DH in mice treated with steroids
-Augmented Th1 cytokines expression in mice treated with steroids[102]SexGenetic relation between sex and susceptibility -Survival of infected animals
-Body weight of the animals
-Detection of quantitative trait loci (QTL)-Reduced body weight and survival in females
-Males and females presented different QTLs associated with the post-infection outcome[103]SexGenetic relation between sex and susceptibility -Bacterial burden in lungs, liver and spleen
-Histological analysis of damaged lungs-Higher bacterial loads in males
-Bigger pulmonary damaged area in males[106,107,108,109]Infection routeCourse of the infection upon aerosol vs.
intravenous administration-Survival of infected animals
-Bacterial burden in lungs, liver and spleen
-Histological analysis of damaged lungs
-Determination of cytokine mRNA profile
-Quantification of IFN-γ producing cells
-M. tuberculosis fitness in the lungs-Higher bacterial loads in mice infected by aerosols
-Reduced survival of mice infected by aerosols
-Higher pulmonary damage in mice infected by aerosols
-Bigger pulmonary granulomas in mice infected by aerosols
-Higher number of IFN-γ producing cells in mice infected intravenously
-Earlier IFN-γ production in mice infected intravenously
-M. tuberculosis fitness after aerosol infection is more realistic that after intravenous infection[110]Infection routeCourse of the infection upon aerosol vs.
intravenous administration-Survival of infected animals
-Bacterial burden in lungs and spleen
-Histological analysis of damaged lungs
-CD4 and CD8 T cells quantification-Reduced survival of one of the mice lineages used after intravenous infection
-Higher bacterial loads in that same lineage
-Reduced number of T cells in that lineage[119,120,121,122]Mice lineageGenetic differences in tuberculosis development between lineages-Survival of infected animals
-Bacterial burden in lungs, spleen and liver
-Histological analysis of damaged lungs
-Detection of quantitative trait loci (QTL)
-Chemokine and cytokine production by lungs
-Functionality of neutrophils-Differences in survival data among different mice lineages
-Differences in bacterial load in each lineage
-Differences in pulmonary pathology displayed in each lineage
-H-2k haplotype is the more susceptible type of mice[123,124,125,129,130,132,136,137,138,139,140,141]Mice lineageC3HeB/FeJ-Survival of infected animals
-Bacterial burden in lungs, spleen and liver
-Histological analysis of damaged lungs
-Polymorphisms mapping
-Determination of cytokine mRNA profile
-Determination of immune cells populations in the lungs-C3HeB/FeJ develops granulomas with central necrosis [123] and hypoxia [125] after intravenous infection
-Upon aerosol infection, this lineage develops different types of lesions [124]
-Polymorphisms in sst1 locus [129,131] and in chromosome 7 [132] are related with enhanced susceptibility
-Neutrophils are responsible of generating the active tuberculosis-like lesions [136,137]
-Host-directed therapies can be tested in this lineage [138,139]
-Cording is a key virulence factor of M. tuberculosis [140]
[143,144,145,146,147,148,149]Mice lineageDBA/2-Survival of infected animals
-Bacterial burden in lungs, spleen and liver
-Histological analysis of damaged lungs
-Polymorphisms mapping
-Determination of cytokine mRNA profile
-Determination of immune cells populations in the lungs-Dissemination of the infection is caused by migration of infected macrophages to uninfected pulmonary tissue [143]
-TRL3 and TRL4 are related to susceptibility against the infection [145]
-Macrophages from this lineage are less able to deal with the infection [146]
-This lineage presents less dendritic and regulatory T cells than other lineages [147]
-Mutants of M. tuberculosis in the synthesis of proline, tryptophan and mycolic acid methyltransferases showed reduced virulence [148,149][151,152,153,155,157,158,159,160,161,162,165,166]Mice lineage129/Sv-Survival of infected animals
-Bacterial burden in lungs, spleen and liver
-Histological analysis of damaged lungs
-Determination of cytokine mRNA profile
-Determination of immune cells populations in the lungs
-Macrophage isolation-Nramp1 [122,151] and Dectin-1 [152] have no effect on resistance to the infection
-Nitric oxide [155,157], TNF-α, IFN-γ [158], IL-6 [159], TAP 1 [160] and TIR8 [161] are necessary to control the infection
-M. tuberculosis can induce the overproduction of foamy macrophages [162]
-Sirtuin 1 can avoid macrophages apoptosis and enhance the control of the infection [165,166][167,169,170,171,172,173,174,175,176,179,180,183,184,185]Mice lineageBALB/c-Survival of infected animals
-Bacterial burden in lungs, spleen and liver
-Histological analysis of damaged lungs
-Determination of cytokine mRNA profile
-Determination of immune cells populations in the lungs-Imbalance of the Th1/Th2 response leads to development of tuberculosis [167]
-BALB/c offers a good latent tuberculosis model for drug testing [169,170,171,172,173]
-IL-4 [174,175,176] and IL-12 [179,180] participate in the Th1/Th2 balance and in the control of the infection
-rv0180 [183] and sigE [184,185] are two new virulence mechanisms of M. tuberculosis[186,187,188,189,190,191,192,193,194,195,196,197,200,201,202,205,206,207,208,209,214,215]Mice lineageC57BL/6-Survival of infected animals
-Bacterial burden in lungs, spleen and liver
-Histological analysis of damaged lungs
-Determination of cytokine mRNA profile
-Determination of immune cells populations in the lungs
-Macrophage isolation-Nitric oxide plays an important role in controlling the infection [186,189]
-C57BL/6 can also be used to recreate the latent tuberculosis scenario where therapeutic vaccines can be tested [180,181,182,183,184,185,186,187,188,189,190,191,192,214,215]
-IL-10 [193], IL-12 [194], and IL-6 [195] are molecules needed to control the infection
-microRNAs control several cellular processes related with susceptibility to the infection [200,201,202,205,206,207,208,209][216,217,218]Unbalanced
immunityHIV and M. tuberculosis co-infection-Bacterial and viral burden in lungs, spleen and liver
-Histological analysis of damaged lungs
-Determination of cytokine profile in the lungs
-Determination of immune cells populations in the lungs-Higher bacterial loads in mice co-infected with both agents
-Disorganized granulomas and increased pulmonary pathology in animals co-infected with both agents
-Increase in the number of neutrophils in the granulomas of co-infected animals
-Increase synthesis of pro-inflammatory cytokines in co-infected animals[219]Unbalanced
immunityInfluenza virus and M. tuberculosis co-infection-Systematic review-Co-infection with both agents worsened the course of tuberculosis [220,223]Unbalanced
immunityCoronavirus and M. tuberculosis
co-infection-Bacterial and viral burden in the lungs
-Determination of immune cells populations and activity in the lungs-Higher bacterial loads in mice co-infected with both agents
-More permissive immune cells populations in co-infected animals [222]Unbalanced
immunityCoronavirus and M. tuberculosis
co-infection-Bacterial and viral burden in lungs, spleen and liver
-Histological analysis of damaged lungs
-Determination of cytokine profile in the lungs
-Determination of immune cells populations in the lungs-No effect of the co-infection upon bacterial load
-No effect of the co-infection upon pulmonary damage
-No effect of the co-infection upon cytokine profile
-No effect of the co-infection upon immune cell populations[227,228]Unbalanced
immunityParasitic and M. tuberculosis
co-infection-Bacterial and parasitic burden in lungs, spleen and liver
-Histological analysis of damaged lungs
-Determination of cytokine profile in the lungs
-Determination of immune cells populations in the lungs-Higher bacterial burden in animals co-infected with helminths
-Higher pulmonary damaged area in animals co-infected with helminths
-Biased immune response towards Th2 type[229,230]UnbalancedimmunityParasitic and M. tuberculosis co-infection-Bacterial and parasitic burden in lungs, spleen and liver
-Histological analysis of damaged lungs
-Determination of cytokine profile in the lungs
-Determination of immune cells populations in the lungs-Non effect or reduced bacterial load in animals co-infected with helminths
-Non effect or reduced pulmonary damaged area in animals co-infected with helminths
-Biased immune response towards Th2 type[233,234]Unbalanced immunityPlasmodium and M. tuberculosis co-infection-Bacterial and parasitic burden in lungs, spleen and liver
-Histological analysis of damaged lungs
-Determination of cytokine profile in the lungs
-Determination of immune cells populations in the lungs-Reduced survival in co-infected animals
-No differences in pulmonary damaged area
-Higher bacterial load in co-infected animals
-Biased immune response towards Th2 type or not efficient Th1 type[237,238,239]UnbalancedimmunityMalnutrition (deficiency)-Survival of infected animals
-Bacterial burden in lungs, spleen and liver
-Histological analysis of damaged lungs
-Determination of cytokine mRNA profile
-Determination of immune cells populations in the lungs, spleen and lymph nodes-Reduced survival in malnourished mice
-Higher bacterial load in malnourished mice
-Poorly structured granulomas formed in malnourished mice
-Initial diminution of nitric oxide, IFN-γ and TNF-α in malnourished mice
-Increased CD4 and CD8 T cells numbers in malnourished mice[242,243,244]UnbalancedimmunityMalnutrition (overnutrition)-Survival of infected animals
-Bacterial burden in lungs, spleen and liver
-Histological analysis of damaged lungs
-Determination of cytokine profile
-Determination of immune cells populations in the lungs
-Intestinal microbiota determination
-Protection efficacy of BCG-Reduced survival in obese mice
-Higher bacterial load in obese mice
-Higher pulmonary damage in obese mice
-Increase in IFN-γ production and inflammatory responses in obese mice
-Higher frequencies of proinflammatory CD4 T cells in obese mice
-Changes in intestinal microbiota could be associated with increased susceptibility[248,250,251]UnbalancedimmunityDiabetes-Survival of infected animals
-Bacterial burden in lungs, spleen and liver
-Histological analysis of damaged lungs
-Determination of cytokine profile
-Determination of immune cells populations in the lungs
-Macrophage isolation and functionality assays-Reduced survival in diabetic mice
-Higher bacterial load in diabetic mice
-Higher pulmonary damage in diabetic mice
-Discordances regarding cytokine profiles
-No differences in the frequencies of T cell populations between groups
-Reduced phagocytic capacity of macrophages from diabetic mice
-Reduced T-cell promoting capacity of macrophages from diabetic mice