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Serum amyloid A proteins reduce bone mass during mycobacterial infections

Gomes, AC; Sousa, DM; Oliveira, TC; Fonseca, O; Pinto, RJ; Silvério, D; Fernandes, AI; Moreira, AC; Silva, T; Teles, MJ; Pereira, L; Saraiva, M

IntroductionOsteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required. MethodsGenetically engineered mice and morphometric, transcriptomic, and functional analyses were used. Additionally, inflammatory mediators and bone turnover markers were measured in the serum of healt...


The neglected contribution of streptomycin to the tuberculosis drug resistance ...

Rocha, DMGC; Viveiros, M; Saraiva, M; Osório, NS

The airborne pathogen Mycobacterium tuberculosis is responsible for a present major public health problem worsened by the emergence of drug resistance. M. tuberculosis has acquired and developed streptomycin (STR) resistance mechanisms that have been maintained and transmitted in the population over the last decades. Indeed, STR resistant mutations are frequently identified across the main M. tuberculosis linea...


Organoids as host models for infection biology – a review of methods

Aguilar, C; Silva, MA; Saraiva, M; Neyazi, M; Olsson, IAS; Bartfeld, S

Infectious diseases are a major threat worldwide. With the alarming rise of antimicrobial resistance and emergence of new potential pathogens, a better understanding of the infection process is urgently needed. Over the last century, the development of in vitro and in vivo models has led to remarkable contributions to the current knowledge in the field of infection biology. However, applying recent advances in ...


Mycobacterium tuberculosis infection up-regulates sialyl lewis x expression in ...

Matos, R; Fonseca, KL; Mereiter, S; Maceiras, AR; Gomes, J; Vilaplana, C; Gärtner, F; Rodrigues, P; Reis, CA; Saraiva, M; Magalhães, A

Glycans display increasingly recognized roles in pathological contexts, however, their impact in the host-pathogen interplay in many infectious diseases remains largely unknown. This is the case for tuberculosis (TB), one of the ten most fatal diseases worldwide, caused by infection of the bacteria Mycobacterium tuberculosis. We have recently reported that perturbing the core-2 O-glycans biosynthetic pathway in...


Heterogeneous Streptomycin Resistance Level Among Mycobacterium tuberculosis St...

Rocha, DMGC; Magalhães, C; Cá, B; Ramos, A; Carvalho, T; Comas, I; Guimarães, JT; Bastos, HN; Saraiva, M; Osório, NS

Widespread and frequent resistance to the second-line tuberculosis (TB) medicine streptomycin, suggests ongoing transmission of low fitness cost streptomycin resistance mutations. To investigate this hypothesis, we studied a cohort of 681 individuals from a TB epidemic in Portugal. Whole-genome sequencing (WGS) analyses were combined with phenotypic growth studies in culture media and in mouse bone marrow deriv...


Interleukin-10 induces interferon-γ-dependent emergency myelopoiesis

Cardoso, A; Martins, AC; Maceiras, AR; Liu, W; Castro, I; Castro, AG; Bandeira, A; Di Santo, JP; Cumano, A; Li, Y; Vieira, P; Saraiva, M

In emergency myelopoiesis (EM), expansion of the myeloid progenitor compartment and increased myeloid cell production are observed and often mediated by the pro-inflammatory cytokine interferon gamma (IFN-γ). Interleukin-10 (IL-10) inhibits IFN-γ secretion, but paradoxically, its therapeutic administration to humans causes hematologic changes similar to those observed in EM. In this work, we use different in vi...


The Expression of Chemokines Is Downregulated in a Pre-Clinical Model of TTR V3...

Moreira, J; Costelha, S; Saraiva, M; Saraiva, MJM

Inflammation is a hallmark of several neurodegenerative disorders including hereditary amyloidogenic transthyretin amyloidosis (ATTRv). ATTRv is an autosomal dominant neurodegenerative disorder with extracellular deposition of mutant transthyretin (TTR) aggregates and fibrils, particularly in nerves and ganglia of the peripheral nervous system. Nerve biopsies from ATTRv patients show increased cytokine producti...


Mycobacterium tuberculosis associated with severe tuberculosis evades cytosolic...

Sousa, J; Cá, B; Maceiras, AR; Simões-Costa, L; Fonseca, KL; Fernandes, AI; Ramos, A; Carvalho, T; Barros, L; Magalhães, C; Chiner-Oms, Á; Machado, H

Genetic diversity of Mycobacterium tuberculosis affects immune responses and clinical outcomes of tuberculosis (TB). However, how bacterial diversity orchestrates immune responses to direct distinct TB severities is unknown. Here we study 681 patients with pulmonary TB and show that M. tuberculosis isolates from cases with mild disease consistently induce robust cytokine responses in macrophages across multiple...


Mycobacterium tuberculosis associated with severe tuberculosis evades cytosolic...

Sousa, J; Cá, B; Maceiras, AR; Simões-Costa, L; Fonseca, KL; Fernandes, AI; Ramos, A; Carvalho, T; Barros, L; Magalhães, C; Chiner-Oms, Á; Machado, H

Genetic diversity of Mycobacterium tuberculosis affects immune responses and clinical outcomes of tuberculosis (TB). However, how bacterial diversity orchestrates immune responses to direct distinct TB severities is unknown. Here we study 681 patients with pulmonary TB and show that M. tuberculosis isolates from cases with mild disease consistently induce robust cytokine responses in macrophages across multiple...


Type I IFN exacerbates disease in tuberculosis-susceptible mice by inducing neu...

Moreira-Teixeira, L; Stimpson, PJ; Stavropoulos, E; Hadebe, S; Chakravarty, P; Ioannou, M; Aramburu, IV; Herbert, E; Priestnall, SL; Suarez-Bonnet, A

Tuberculosis (TB) is a leading cause of mortality due to infectious disease, but the factors determining disease progression are unclear. Transcriptional signatures associated with type I IFN signalling and neutrophilic inflammation were shown to correlate with disease severity in mouse models of TB. Here we show that similar transcriptional signatures correlate with increased bacterial loads and exacerbate pat...


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