Increased intracellular survival of Salmonella Typhimurium ST313 in HIV‐1‐infected primary human macrophages is not associated with Salmonella hijacking the HIV compartment

Abstract

Background Non‐typhoidal Salmonella (NTS) causes a severe invasive syndrome (iNTS disease) described in HIV‐positive adults. The impact of HIV‐1 on Salmonella pathogenesis and the molecular basis for the differences between these bacteria and classical diarrhoeal S. Typhimurium remains unclear. Results Here, we show that iNTS‐associated S. Typhimurium Sequence Type 313 (ST313) bacteria show greater intracellular survival in primary human macrophages, compared with a ‘classical’ diarrhoeal S. Typhimurium ST19 isolate. The increased intracellular survival phenotype of ST313 is more pronounced in HIV‐infected macrophages. We explored the possibility that the bacteria take advantage of the HIV‐associated viral‐containing compartments created in human macrophages that have low pH. Confocal fluorescence microscopy and focussed ion beam‐scanning electron microscopy tomography showed that Salmonella did not co‐localise extensively with HIV‐positive compartments. Conclusion The capacity of ST313 bacteria to survive better than ST19 bacteria within primary human macrophages is enhanced in cells pre‐infected with HIV‐1. Our results indicate that the ST313 bacteria do not directly benefit from the niche created by the virus in HIV‐1‐infected macrophages, and that they might take advantage from a more globally modified host cell. Significance A better understanding of the interplay between HIV‐1 and Salmonella is important not only for these bacteria but also for other opportunistic pathogens.

Evolutionary dynamics of multidrug resistant Salmonella enterica serovar 4,[5],12:i:- in Australia

“…Typhimurium ST313 demonstrated a correlation between lower FliC expression, reduced inflammatory responses, and enhanced survival in macrophages; these phenotypes were linked to the high invasiveness and bacteremia associated with clinical S . Typhimurium ST313 infections 56 – 58 . One caveat of these studies, however, was that conclusions were drawn from the comparison of in vitro cellular responses between ST313 and ST19 isolates, two distinct lineages of NTS.…”

IL4I1 binds to TMPRSS13 and competes with SARS-CoV-2 spike

“…Monocyte-derived macrophages (hMDMs) were differentiated from PBMCs according to the method described in Lê-Bury et al. ( 39 ) for six days. CD3 + cells and naïve B cells were isolated from donor PBMCs using the magnetic bead Pan T isolation kit and B Cell Isolation Kit II from Miltenyi respectively, according to the manufacturer’s instructions.…”

“…Peripheral blood mononuclear cells (PBMCs) were obtained by cytapheresis from healthy donors from the French Blood bank (Etablissement Francais du sang, EFS) and isolated using a Ficoll density gradient. Monocyte-derived macrophages (hMDMs) were differentiated from PBMCs according to the method described in Le-Bury et al (39) for six days. CD3 + cells and naïve B cells were isolated from donor PBMCs using the magnetic bead Pan T isolation kit and B Cell Isolation Kit II from Miltenyi respectively, according to the manufacturer's instructions.…”

HIV and Mediterranean Zoonoses: A Review of the Literature

“…The severity of iNTS in PLWH may be due to an impaired immune response to the infection, as suggested in a study by MacLennan et al [ 84 ]; specifically, it was reported that an excess of antibodies against Salmonella lipopolysaccharide (LPS) is associated with a reduction in Salmonella killing. Other reasons behind the severity of iNTS in PLWH may be found in the dysregulation of proinflammatory cytokine release, such as TNF alpha, IL-10 and IL-12 [ 85 ], the attenuation of transcription factor nuclear κB (NFκB)-mediated inflammation [ 86 ], the defective activity of monocytes phagocytosis [ 87 ] and the apparent enhanced capacity of a specific sequence type 313 (ST313) of S. typhimurium of surviving in HIV-infected macrophages and their defective phagocytic ability [ 88 , 89 ].…”