Abstract
Granulomas are compact structures formed in tissues by the immune system in response to aggressions. The in vitro formation of granulomas using circulating mononuclear cells is an innovative method to easily assess the immune response of patients. Monitoring the efficiency of mononuclear cells from patients to form granulomas in vitro would help improve their therapeutic management. Circulating mononuclear cells from 23 elderly patients with sepsis and 24 elderly controls patients were incubated with Sepharose beads coated with either BCG or Coxiella burnetii extracts. The formation of granulomas was measured over 9 days. Most healthy elderly patients (92%) were able to form granulomas in response to BCG and Coxiella burnetii extracts compared to only 48% of infected elderly patients. Undernutrition was significantly associated with impaired granuloma formation in healthy and infected patients. Granulomas typically comprise epithelioid cells and multinucleated giant cells, however, these cells were not detected in samples obtained from patients unable to form granulomas. We also found that the impairment of granuloma formation was associated with reduced production of tumor necrosis factor without overproduction of interleukin-10. Finally, all genes specifically modulated in granulomatous cells were down-modulated in patients with defective granuloma formation. TNFSF10 was the only M1 gene markedly upregulated in patients who did not form granulomas. Our study suggest that defective granuloma formation may be a measurement of altered activation of immune cells which can predispose to nosocomial infections in elderly patients.
Highlights
Granulomas are organized collections of immune cells that reflect tissue immune response to aggressions (Saunders and Britton, 2007; Herndon and Rogers, 2013; Pagán and Ramakrishnan, 2018)
We hypothesized that the efficiency of mononuclear cells from infected patients to form granulomas in vitro was lower compared to elderly controls which can predispose to nosocomial infections
The comparison of granuloma formation in response to BCG and Coxiella burnetii (CB) extracts did not show any significant difference, except at day 9 for controls for whom the granuloma percentage was significantly lower in response to CB extracts than in response to BCG (Figure 2). These results show that the ability to develop an in vitro granulomatous response to BCG or CB extracts was altered in infected elderly patients
Summary
Granulomas are organized collections of immune cells that reflect tissue immune response to aggressions (Saunders and Britton, 2007; Herndon and Rogers, 2013; Pagán and Ramakrishnan, 2018). CD4+ T cells differentiate into T helper type 1 (Th1) effector cells that secrete IFN-γ and TNF; these mediate protection by stimulating the anti-microbial activity of macrophages (Saunders and Britton, 2007). In humans, impaired IL12/IFN-γ predisposes patients to mycobacterial infections and interferes with granuloma formation depending on the severity of IFN-γ impairment (Naranbhai, 2016)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
