Biology subjects

Persson, J. J.

Publications and source records attributed to Persson, J. J..

3 recordsLinked to original sources

bioRxiv2026

Macrophages reshape cytokine responses and bacterial spatial organization in an airway epithelial cell culture model

The increasing prevalence of antibiotic-resistant bacterial infections highlights the need for physiologically relevant in vitro models that recapitulate host-pathogen interactions. Pseudomonas aeruginosa is a clinically important opportunistic pathogen associated with hospital-acquired infections and chronic airway diseases, including cystic fibrosis, where dysregulated inflammatory responses contribute to disease progression. While air-liquid interface (ALI) models have advanced the study of airway epithelium, most of these modes lack immune components, limiting their ability to capture immune-epithelial interactions. Here, we expanded a previously established dual-cell ALI model incorporating human monocyte-derived macrophages to investigate how immune context, bacterial dose, and time influence early infection dynamics. Standard BCi-NS1.1 epithelial monocultures and macrophage co-cultures were infected with P. aeruginosa (PAO1) at low (100 colony-forming units (CFU) and high (1000 CFU) inoculum and analyzed over 10, 16, and 24 h post-infection (hpi). Macrophage presence did not significantly alter total bacterial burden but markedly influenced cytokine responses and bacterial spatial organization. Pro-inflammatory cytokines (interleukin (IL)-1, IL-1{beta}, Tumor Necrosis Factor (TNF)-) were enhanced in dual-cell culture models, while IL-6 exhibited a threshold-dependent response detectable only at higher bacterial loads. Confocal imaging revealed that macrophages altered bacterial distribution, promoting a more dispersed pattern compared to the clustered organization observed in epithelial monocultures. These effects were most pronounced at lower bacterial inocula. Together, our findings demonstrate that macrophages reshape early infection dynamics by modulating inflammatory signaling and bacterial spatial organization without affecting overall bacterial burden. This study highlights the importance of incorporating immune cells into in vitro airway models.

immunology↗

bioRxiv2026

Host-microbe-immune interactions in an air-liquid interface airway model

BackgroundAir-liquid interface (ALI) cell culture systems have improved the study of host-microbe interactions in respiratory infections. However, most ALI models lack immune components, limiting their ability to capture epithelial-immune crosstalk. To address this, we developed a dual-cell ALI model incorporating human peripheral blood monocyte-derived macrophages beneath differentiated airway epithelial cells. MethodologyMacrophages were seeded on the basolateral side of transwell inserts using fibronectin coating. Model characterization included transepithelial electrical resistance (TEER) to assess epithelial barrier integrity, IL-8 secretion as a marker of epithelial inflammatory signaling, and confocal microscopy to evaluate cellular architecture before and after infection. Mono-and dual-cell cultures were infected with the laboratory strain Pseudomonas aeruginosa PAO1. ResultsMacrophages adhered stably to the basolateral surface without compromising epithelial barrier integrity. Following infection, IL-8 secretion was elevated in epithelial monocultures compared to dual-cell cultures, suggesting early immune modulation in the presence of macrophages. While overall bacterial burden was comparable, confocal imaging revealed clustered bacterial growth in monocultures and a more dispersed spatial distribution in dual-cell cultures. ConclusionsThis dual-cell ALI model enables investigation of early epithelial-immune interactions, inflammatory modulation, and bacterial colonization dynamics during airway infection. The system provides a versatile and human-relevant platform for studying respiratory host-pathogen interactions.

cell biology↗

bioRxiv2023

Protection conferred by intraperitoneal Group A Streptococcus immunization relies on macrophages and IFN-γ but not on concurrent adaptive immune responses.

Group A Streptococcus (GAS; Streptococcus pyogenes) is an important bacterial pathogen estimated to cause over 700 million superficial infections and around 500.000 deaths due to invasive disease or severe post-infection sequelae in the world yearly. In spite of this major impact on society, there is currently no vaccine available against this bacterium. GAS strains can be separated into >200 distinct emm (M)-types, and protective immunity against GAS is believed to in part be dependent on type-specific antibodies. Here, we analyze the nature of protective immunity generated against GAS in a model of intraperitoneal immunization in mice. We demonstrate that multiple immunizations are required for the ability to survive a subsequent lethal challenge, and although significant levels of GAS-specific antibodies are produced, these are redundant for protection. Instead, our data show that the immunization-dependent protection in this model is induced in the absence of B and T cells, is accompanied by an altered cytokine profile upon subsequent infection and requires macrophages and the macrophage-activating cytokine IFN-{gamma}. To our knowledge these findings are the first to suggest that GAS has the ability to induce forms of trained innate immunity. Taken together, the current study reveals a novel mechanism of the innate immune system in response to GAS infections that potentially could be leveraged for future development of effective vaccines. Author summaryThe bacterium Group A Streptococcus (GAS) causes many hundred million infections and around 500.000 deaths in the world every year. GAS can give rise to a wide spectrum of diseases ranging from mild strep throat to life-threatening necrotizing fasciitis (often referred to as "flesh-eating disease"). There is currently no vaccine available for this pathogen, much due to our incomplete knowledge of how the immune system reacts to different GAS infections, what immune responses are in fact required for long-term protection and how these are generated. Here we show that protective immunity arising after immunization through the intraperitoneal (ip) cavity requires multiple injections using heat killed GAS. Surprisingly, although typical adaptive immune responses are activated and generate production of GAS-specific antibodies these are redundant for protection, which instead hinges on macrophages and the cytokine IFN-{gamma}. Our findings suggest that ip GAS immunizations trigger what is known as trained immunity, where innate immune cells become imprinted to respond with increased efficiency towards subsequent infection. Overall, these observations highlight a previously unknown ability of GAS to induce non-canonical forms of protective immunity, discoveries that may significantly contribute to our thinking about how the immune system reacts to such infections and broaden the scope for future vaccine strategies.

immunology↗