Perspective on Animal Models: Chronic Intracellular Infections

Young, Lowell S.; Bermudez, Luiz E.

doi:10.1086/321851

Cited by 10 publications

(5 citation statements)

References 29 publications

(27 reference statements)

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“…A MAC-infected C3HeB/FeJ mouse model is supported by other murine studies showing early in vivo expression of IFN-γ during MAC - infection correlated with resistance to the infection (Gangadharam, 1995; Young and Bermudez, 2001; Appelberg, 2006). The use of specific neutralizing antibodies in vivo led to the identification of IFN-γ and TNF-α as protective cytokines acting at the effector level of resistance to MAC (Gangadharam, 1995; Young and Bermudez, 2001; Appelberg, 2006).…”

Section: Discussionmentioning

confidence: 59%

Mycobacterium avium Infection in a C3HeB/FeJ Mouse Model

et al. 2019

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Infections caused by Mycobacterium avium complex (MAC) species are increasing worldwide, resulting in a serious public health problem. Patients with MAC lung disease face an arduous journey of a prolonged multidrug regimen that is often poorly tolerated and associated with relatively poor outcome. Identification of new animal models that demonstrate a similar pulmonary pathology as humans infected with MAC has the potential to significantly advance our understanding of nontuberculosis mycobacteria (NTM) pathogenesis as well as provide a tractable model for screening candidate compounds for therapy. One new mouse model is the C3HeB/FeJ which is similar to MAC patients in that these mice can form foci of necrosis in granulomas. In this study, we evaluated the ability of C3HeB/FeJ mice exposure to an aerosol infection of a rough strain of MAC 2285 to produce a progressive infection resulting in small necrotic foci during granuloma formation. C3HeB/FeJ mice were infected with MAC and demonstrated a progressive lung infection resulting in an increase in bacterial burden peaking around day 40, developed micronecrosis in granulomas and was associated with increased influx of CD4 + Th1, Th17, and Treg lymphocytes into the lungs. However, during chronic infection around day 50, the bacterial burden plateaued and was associated with the reduced influx of CD4 + Th1, Th17 cells, and increased numbers of Treg lymphocytes and necrotic foci during granuloma formation. These results suggest the C3HeB/FeJ MAC infection mouse model will be an important model to evaluate immune pathogenesis and compound efficacy.

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Section: Discussionmentioning

confidence: 59%

Mycobacterium avium Infection in a C3HeB/FeJ Mouse Model

et al. 2019

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“…The stomach was traditionally thought to be a barrier to mycobacteria, but it was shown that virulent M. avium strains could infect mice orally and be found in gut lymphoid tissues [21,22]. If the beige mutant in the C57BL/6 mouse was used, this was amplified [21,22]. Our laboratory has also found that SCID mice infected orally with M. abscessus resulted in a progressive infection (Ordway D et al, [18] unpublished observations).…”

Section: Routes Of Infection In Animal Modelsmentioning

confidence: 99%

Section: Routes Of Infection In Animal Modelsmentioning

confidence: 99%

Animal Models of Non-Tuberculous Mycobacterial Infections

Chan¹,

Bai²,

Ordway³

et al. 2016

Mycobact Dis

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The use of animal models has been essential in understanding the pathogenesis of and hosts immune response to tuberculosis, as well as testing potential antimicrobial compounds and vaccines. Experimental animals have also been used to study infections due to non-tuberculous mycobacteria (NTM). Because there are many different species of NTM capable of causing disease and they have varying degrees of virulence, developing animal models that are suitable for the diseases they cause isolated lung disease, skin and soft-tissue infections, and visceral extra pulmonary /disseminated disease is challenging. The goal of this review is to discuss the various animal models that have been used to study the pathogenesis of NTM infection as well as screening candidate antimicrobials, which are essential endeavors if better control of NTM infection is to be achieved.

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“…However, if beige mice with C57BL/6 background were used, the degree of infection was further increased [68,69]. Additional studies showed that M. avium accessed the gut epithelium by interactions with enterocytes [69].…”

Section: Evidence For Ntm Interference With Bcg Efficacymentioning

confidence: 99%

Non-Tuberculous Mycobacteria Interference with BCG-Current Controversies and Future Directions

2020

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The global tuberculosis (TB) epidemic caused by the bacterial pathogen Mycobacterium tuberculosis (M.tb) continues unabated. The Mycobacterium bovis bacillus Calmette–Guérin (BCG) vaccination is widely utilized worldwide to protect against infection with M.tb. BCG vaccine protection against TB has had widely varying results for reasons that are not well understood. BCG vaccine interference by non-tuberculosis (NTM) mycobacterial species has been implicated as the potential cause of reduced BCG vaccine efficacy against M.tb. Ongoing efforts to develop new vaccines for TB requires a thorough understanding of the effect of NTM exposure on BCG vaccine efficacy, which may ultimately be a critical determinant of success. We reviewed the conflicting reports on whether NTM interferes with the BCG vaccine, potential explanations to help resolve the controversy, and strategies for developing better animal models. Further studies are needed to longitudinally track the effects of NTM exposure on BCG vaccine-induced host-protective anti-TB immunity.

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Perspective on Animal Models: Chronic Intracellular Infections

Cited by 10 publications

References 29 publications

Mycobacterium avium Infection in a C3HeB/FeJ Mouse Model

Mycobacterium avium Infection in a C3HeB/FeJ Mouse Model

Animal Models of Non-Tuberculous Mycobacterial Infections

Non-Tuberculous Mycobacteria Interference with BCG-Current Controversies and Future Directions

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