preparation-agar-bead-embedded-mycobacterium-abscessus-to-inoculate

Preparation of Agar Bead Embedded <em>Mycobacterium abscessus</em> to Inoculate Immunocompetent Mice Intratracheally

Robust mouse models of chronic infection with Mycobacterium abscessus, an environmental pathogen that preferably infects the lungs, are badly needed. ...

IRCCS San Raffaele Scientific Institute

The human immunodeficiency virus type-1 (HIV-1) establishes a state of latent infection in a small number of CD4 T lymphocytes that, nonetheless, represent a major obstacle to viral eradication. We here show that Tripartite Motif-containing protein 22 (TRIM22), an epigenetic inhibitor of Specificity protein 1 (Sp1)-dependent HIV-1 transcription, is a relevant factor in maintaining a state of repressed HIV-1 expression at least in CD4 T cell lines. By knocking-down (KD) TRIM22 expression, we observed an accelerated reactivation of a doxycycline (Dox)-controlled HIV-1 replication in the T lymphocytic SupT1 cell line. Furthermore, we here report for the first time that TRIM22 is a crucial factor for maintaining a state of HIV-1 quiescence in chronically infected ACH2 -T cell line while its KD potentiated HIV-1 expression in both ACH-2 and J-Lat 10.6 cell lines upon cell stimulation with either tumor necrosis factor-α (TNF-α) or histone deacetylase inhibitors (HDACi). In conclusion, TRIM22 is a novel determinant of HIV-1 latency, at least in T cell lines, thus representing a potential pharmacological target for strategies aiming at curtailing or silencing the pool of latently infected CD4 T lymphocytes constituting the HIV-1 reservoir in individuals receiving combination antiretroviral therapy.

Interferon-inducible TRIM22 contributes to maintenance of HIV-1 proviral latency in T cell lines.

Hepcidin levels predict Covid-19 severity and mortality in a cohort of hospitalized Italian patients.

Nontypeable  (NTHi) is commonly isolated from airways of patients suffering from chronic respiratory diseases, such as COPD or cystic fibrosis (CF). However, to what extent NTHi long-term infection contributes to the lung inflammatory burden during chronic airway disease is still controversial. Here, we exploited human respiratory samples from a small cohort of CF patients and found that patients chronically infected with NTHi had significantly higher levels of interleukin (IL)-8 and CXCL1 than those who were not infected. To better define the impact of chronic NTHi infection in fuelling inflammatory response in chronic lung diseases, we developed a new mouse model using both laboratory and clinical strains. Chronic NTHi infection was associated with chronic inflammation of the lung, characterised by recruitment of neutrophils and cytokine release keratinocyte-derived chemokine (KC), macrophage inflammatory protein 2 (MIP-2), granulocyte colony-stimulating factor (G-CFS), IL-6, IL-17A and IL-17F) at 2 and 14 days post-infection. An increased burden of T-cell-mediated response (CD4 and γδ cells) and higher levels of pro-matrix metalloproteinase 9 (pro-MMP9), known to be associated with tissue remodelling, were observed at 14 days post-infection. Of note we found that both CD4IL-17 cells and levels of IL-17 cytokines were enriched in mice at advanced stages of NTHi chronic infection. Moreover, by immunohistochemistry we found CD3, B220 and CXCL-13 cells localised in bronchus-associated lymphoid tissue-like structures at day 14. Our results demonstrate that chronic NTHi infection exerts a pro-inflammatory activity in the human and murine lung and could therefore contribute to the exaggerated burden of lung inflammation in patients at risk.

Chronic infection by nontypeable  fuels airway inflammation.

Host inflammation contributes to determine whether SARS-CoV-2 infection causes mild or life-threatening disease. Tools are needed for early risk assessment.

CXCL10 levels at hospital admission predict COVID-19 outcome: hierarchical assessment of 53 putative inflammatory biomarkers in an observational study.

The incidence of lung infections is increasing worldwide in individuals suffering from cystic fibrosis and chronic obstructive pulmonary disease. Mycobacterium abscessus is associated with chronic lung deterioration in these populations. The intrinsic resistance of M. abscessus to most conventional antibiotics jeopardizes treatment success rates. To date, no single drug has been developed targeting M. abscessus specifically. The objective of this study was to characterize VOMG, a pyrithione-core drug-like small molecule, as a new compound active against M. abscessus and other pathogens.

The novel drug candidate VOMG kills Mycobacterium abscessus and other pathogens by inhibiting cell division.

SARS-CoV-2 pandemic still poses a significant burden on global health and economy, especially for symptoms persisting beyond the acute disease. COVID-19 manifests with various degrees of severity and the identification of early biomarkers capable of stratifying patient based on risk of progression could allow tailored treatments.

The longitudinal characterization of immune responses in COVID-19 patients reveals novel prognostic signatures for disease severity, patients' survival and long COVID.

Article	Year
Interferon-inducible TRIM22 contributes to maintenance of HIV-1 proviral latency in T cell lines. Virus research\| PubMed ID: 31136823	2019
Hepcidin levels predict Covid-19 severity and mortality in a cohort of hospitalized Italian patients. American journal of hematology\| PubMed ID: 33075189	2021
Chronic infection by nontypeable fuels airway inflammation. ERJ open research\| PubMed ID: 33778054	2021
CXCL10 levels at hospital admission predict COVID-19 outcome: hierarchical assessment of 53 putative inflammatory biomarkers in an observational study. Molecular medicine (Cambridge, Mass.)\| PubMed ID: 34663207	2021
The novel drug candidate VOMG kills Mycobacterium abscessus and other pathogens by inhibiting cell division. International journal of antimicrobial agents\| PubMed ID: 39069229	2024
The longitudinal characterization of immune responses in COVID-19 patients reveals novel prognostic signatures for disease severity, patients' survival and long COVID. Frontiers in immunology\| PubMed ID: 39136010	2024

Fabio Saliu

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