bims-ainimu 2026-03-01 papers

bims-ainimu

Biomed News

on AI & infection immunometabolism

Issue of 2026–03–01
eight papers selected by
Pedro Escoll Guerrero, Institut Pasteur

Complex I preserves mitochondrial polarization during infection of human macrophages by secretion-competent bacteria.
Current Applications and Immunological Considerations of Salmonella enterica Serovar Typhimurium as a Vaccine Vector.
Macrophage Metabolic Reprogramming-Related Osteoimmunity in Osteoporosis.
Host-pathogen interactions during early stages of bovine mastitis: divergent macrophage responses to distinct bovine-associated Staphylococci species and strains.
Mitochondrial Quality Control in Macrophages during Cardiovascular Disease.
A Novel Loop-Mediated Isothermal Amplification (LAMP) Primer Set for Detecting the STY2879 Gene of Salmonella enterica Serovar Typhi in Raw Milk.
Organic acids - a dual-action mode influencing both host and pathogen integrity to reduce Salmonella infection.
Dysregulated Copper Metabolism-Induced Cuproptosis Contributes to Mitochondrial Dysfunction and Macrophage Inflammatory Response in Acute Lung Injury.

Infect Immun. 2026 Feb 27. e0049525

Complex I preserves mitochondrial polarization during infection of human macrophages by secretion-competent bacteria.

Francisco-Javier Garcia-Rodriguez, Paula Martinez-Oca, Carmen Buchrieser, Pedro Escoll.

  Intracellular bacteria remodel host bioenergetics and modulate mitochondrial membrane potential (Δψm). However, how individual electron transport chain (ETC) components sustain Δψm during infection of primary human macrophages remains unclear. Here, we combined extracellular flux analysis with single-cell live imaging to understand how the ETC functions in human monocyte-derived macrophages during infection with Legionella pneumophila (Lp) or Salmonella enterica serovar Typhimurium (S.Tm). At 5 h post-infection, the Lp type IV secretion system (T4SS) and the S.Tm SPI-1 T3SS were required for the early drop of the oxygen consumption rate. Despite reduced respiration, the Δψm was preserved in all infection conditions, and pathogen-specific strategies to maintain the Δψm were revealed. While Lp infection modulates the FOF1-ATPase to function in the reverse mode (hydrolase), with the adenine-nucleotide translocator remaining in forward mode, S.Tm does not reverse the FOF1-ATPase during infection. Systematic inhibition of ETC complexes established that Complex I is uniquely required to maintain the Δψm during infection with virulent bacteria, but not with secretion-deficient mutant strains. Complex II is required in all infection conditions, but its inhibition had a minimal effect in non-infected cells, indicating infection-driven participation of this complex in the electron flow in the ETC, coupled with the preservation of the Δψm. Complexes III and IV were essential in infected and non-infected cells. Together, our results identify a Complex I-driven maintenance of the Δψm, establishing Complex I as a bioenergetic checkpoint that distinguishes virulent from secretion-deficient intracellular bacteria. Furthermore, we reveal that divergent strategies are employed by Lp and S.Tm to preserve mitochondrial polarization of macrophages early during infection.

Keywords:  Legionella pneumophila; Salmonella Typhimurium; electron transport chain; macrophages; mitochondria; virulence

DOI:  https://doi.org/10.1128/iai.00495-25
Microorganisms. 2026 Feb 18. pii: 492. [Epub ahead of print]14(2):

Current Applications and Immunological Considerations of Salmonella enterica Serovar Typhimurium as a Vaccine Vector.

Adam S Hassan, Kaitlin Winter, Charles M Dozois, Brian J Ward, Momar Ndao.

  Live attenuated Salmonella enterica serovar Typhimurium has been investigated for decades as an orally delivered vaccine vector due to its ability to target the intestinal mucosa and engage both innate and adaptive immune responses. In humans, S. Typhimurium infection is largely restricted to the gastrointestinal tract, distinguishing it from Salmonella Typhi and providing a rationale for its use in mucosal vaccine strategies. In this review, we discuss the biological features of S. Typhimurium that support its use as a vaccine vector and summarize current understanding of the immune responses generated during wild-type infection, including innate activation and downstream T cell and B cell responses. We compare key biological differences between Salmonella Typhi and S. Typhimurium and outline emerging vector design strategies, including delayed attenuation and chromosomal integration of heterologous antigens. We then review applications of attenuated S. Typhimurium vectors targeting viral, bacterial, and parasitic pathogens, highlighting shared immunological outcomes and design principles across platforms. Finally, we discuss recent advances in vector engineering, including chromosomal integration of heterologous antigens, as well as remaining gaps in knowledge related to the durability of immune responses and translational considerations.

Keywords:  Salmonella enterica serovar Typhimurium; host–pathogen interactions; live attenuated vaccines; mucosal immunity; vaccine vectors

DOI:  https://doi.org/10.3390/microorganisms14020492
Calcif Tissue Int. 2026 Feb 24. pii: 35. [Epub ahead of print]117(1):

Macrophage Metabolic Reprogramming-Related Osteoimmunity in Osteoporosis.

Kejia Zhou, Zhenpeng Wang, Mei Zhang.

  Osteoporosis is a disease characterized by increased bone turnover and decreased bone mass, closely associated with suppressed osteogenesis, enhanced osteoclastogenesis, and immune-metabolic dysregulation. Studies in osteoimmunology have shown that immune dysregulation can disrupt bone homeostasis through multiple signaling pathways and metabolic interactions between immune cells and bone cells. Macrophages, as key players in osteoimmunity, dynamically alter their metabolism in specific environments, integrating environmental signals to exhibit context-specific functions. Among the primary metabolic phenotypes, classically activated macrophages (M1) mainly promote bone resorption, while alternatively activated macrophages (M2) primarily facilitate osteogenesis. These effects are mainly achieved through inflammatory pathways, macrophage-driven osteoclastogenesis, and efferocytosis. Dysregulation of macrophage metabolic reprogramming in osteoimmunity can lead to diseases such as osteoporosis. The link between metabolic reprogramming and epigenetic modifications is a research hotspot in immune-metabolic diseases, and targeting macrophage metabolic reprogramming has shown potential therapeutic benefits for osteoporosis. This review discusses the impact of macrophage metabolic reprogramming-related osteoimmune pathways on osteoporosis.

Keywords:  Macrophages; Metabolic reprogramming; Osteoimmunity; Osteoporosis

DOI:  https://doi.org/10.1007/s00223-026-01477-y
Braz J Microbiol. 2026 Feb 22. pii: 57. [Epub ahead of print]57(1):

Host-pathogen interactions during early stages of bovine mastitis: divergent macrophage responses to distinct bovine-associated Staphylococci species and strains.

Sarah Antonieta de Oliveira Veríssimo, Ygor Fagundes Ruas, Filipe Aguera Pinheiro, Luiza Campos Reis, Bernardina Amorim Uscata, Hiro Goto, Soraia Araújo Diniz, Adriana Cortez, Sarne De Vliegher, Marcos Bryan Heinemann, Eduardo Milton Ramos-Sanchez, Fernando Nogueira de Souza, Mônica Maria Oliveira Pinho Cerqueira.

   BACKGROUND: Bovine mastitis is the most economically significantdisease in dairy farming, with Staphylococcus aureus and Staphylococcus chromogenes asprominent agents, the former posing a major threat. As principal immune sentinels in themammary gland, macrophages orchestrate early pathogen recognition and immune activation,critically influencing the trajectory and outcome of infection. Thus, this study aimed tocharacterize the early macrophage responses to distinct bovine-associated S. aureus and S.chromogenes strains.
METHODS: Here, RAW 264.7 cells were challenged with four differentstrains: S. aureus [isolated from nose (SN), and intramammary infection (IMI)] and S.chromogenes [IMI, and teat apex (TA)] were evaluated after 90- and 180-min. Nitric oxide (NO)production was analyzed in the supernatants, and mRNA levels of IL-1β, IL-18, NLRP3, NOS2,Arg1, Bax, and Bcl2 were assessed in the cells.
RESULTS: Macrophages challenged with S. aureusIMI strains showed elevated Nos2 expression but negligible NO production, indicating a potentialimmune evasion mechanism. The commensal S. aureus SN strain uniquely maintained arginaseexpression, suggesting M2-like polarization that may promote immune tolerance and bacterialcolonization. Both S. aureus strains significantly upregulated the anti-apoptotic Bcl2 gene, atranscriptional response that may be associated with host cell survival, which may facilitatebacterial intracellular persistence. In contrast, S. chromogenes strains induced strong NOS2expression, robust NLRP3 inflammasome activation, and increased IL-1β production, indicatingM1 polarization and a pro-inflammatory response. The pro-apoptotic Bax gene showed an earlydecrease followed by a later increase exclusively in S. aureus-infected macrophages, indicating atime-dependent transcriptional modulation of apoptosis-related genes.
CONCLUSIONS: Thesegenotype-dependent macrophage responses reveal complex immune modulation shaping mastitis pathogenesis. However, our findings are based solely on transcriptional data on the murine cells and require further validation.

Keywords:  Dairy cow; Immune response; Mastitis; Non-aureus staphylococci; Staphylococcus aureus

DOI:  https://doi.org/10.1007/s42770-026-01888-x
Can J Cardiol. 2026 Feb 23. pii: S0828-282X(26)00152-2. [Epub ahead of print]

Mitochondrial Quality Control in Macrophages during Cardiovascular Disease.

Ryan C Falconer, Emily A Day.

  Macrophages are key cells of the innate immune system. Within the cardiovascular system, macrophages exhibit marked phenotypic plasticity, enabling them to sense local cues and regulate vascular inflammation, myocardial injury, and tissue remodeling. Mitochondria serve as multifunctional organelles in macrophages, integrating cellular metabolism with the production of immunogenic signals that shape inflammatory responses. In cardiovascular disease (CVD), mitochondrial dysfunction in macrophages drives maladaptive inflammatory responses that when unresolved, lead to chronic inflammation and tissue injury underlying adverse cardiovascular outcomes. To preserve mitochondrial integrity under diverse conditions, cells engage an interconnected network of mitochondrial quality control (MQC) mechanisms, namely mitochondrial biogenesis, maintenance of mitochondrial DNA (mtDNA), remodelling by fission and fusion, mitophagy, and the mitochondrial unfolded protein response. This review examines how these MQC systems govern macrophage polarization, inflammatory signalling, and survival in CVD, focusing on atherosclerosis, myocardial infarction, and heart failure. We discuss evidence demonstrating that the dysregulation of these mechanisms in macrophages, contributes to cardiovascular impairment, with particular emphasis on how dysregulated mitochondrial dynamics, heightened mitochondrial oxidative stress, and mtDNA release converge to amplify inflammation in CVD. We further highlight clinical evidence suggesting that current therapies, such as statins, SGLT2 inhibitors, and GLP-1 receptor agonists enhance macrophage MQC to alleviate stress, improve metabolic function, and dampen inflammation, which may contribute to their cardiovascular benefit. By examining the role of MQC in macrophages within the cardiovascular system, this review establishes the mechanisms governing mitochondrial homeostasis and dysfunction as a critical immunometabolic axis and potential therapeutic avenue underlying cardiovascular disease.

Keywords:  Immunometabolism; Macrophages; Mitochondria; Mitochondrial Quality Control; cGAS-STING

DOI:  https://doi.org/10.1016/j.cjca.2026.02.034
Microorganisms. 2026 Jan 27. pii: 297. [Epub ahead of print]14(2):

A Novel Loop-Mediated Isothermal Amplification (LAMP) Primer Set for Detecting the STY2879 Gene of Salmonella enterica Serovar Typhi in Raw Milk.

Hyuck-Jin Seo, Timothy E Riedel.

  Milk-borne outbreaks remain a significant issue in low-income countries due to unhygienic practices. Currently, there are no known easily accessible and low-cost diagnostic tests that can detect Salmonella enterica subsp. enterica serovar Typhi, the causative agent of typhoid fever, in raw milk samples at high specificity, sensitivity, and speed without preprocessing. Early detection of Salmonella enterica subsp. enterica serovar Typhi in food matrices is critical for preventing infection prior to consumption and reducing disease burden. Using colorimetric loop-mediated isothermal amplification, we screened 15 novel and two previously published primer sets. We identified one novel primer set capable of detecting the STY2879 gene in as few as 2000 genomes in 2% v/v raw milk reactions and 1000 genomes in 1% v/v raw milk reactions of Salmonella enterica subsp. enterica serovar Typhi after 30 minutes of incubation in a 65° C water bath. The colorimetric readout offers promising potential applications for on-site detection in remote and low-resource settings where infection with Salmonella enterica subsp. enterica serovar Typhi remains a public health concern.

Keywords:  LAMP; STY2879; Salmonella; Typhi; detection; diagnostic; enterica; field test; loop-mediated isothermal amplification; primer set; raw milk; serovar; typhoid fever; unpasteurized

DOI:  https://doi.org/10.3390/microorganisms14020297
Microb Pathog. 2026 Feb 25. pii: S0882-4010(26)00132-4. [Epub ahead of print] 108406

Organic acids - a dual-action mode influencing both host and pathogen integrity to reduce Salmonella infection.

Diana Marcu, Igori Balta, Ozan Gundogdu, Adela Marcu, Todd Callaway, Tiberiu Iancu, Ioan Pet, Florica Morariu, Lavinia Stef, Nicolae Corcionivoschi.

  In this study, we aimed to describe the mechanism by which a blend of organic acids (AuraShield - As) prevents Salmonella Typhimurium SE10/72 infection of primary chicken caecal epithelial cells (PECC) and caecal biopsies. First, our results show a MIC of 0.50% and an MBC of 1% against Salmonella Typhimurium SE10/72, with a sub-inhibitory concentration of 0.25% selected for further experiments. At this level, in vitro and ex vivo, As significantly decreased the ability of S. Typhimurium to attach to and invade PECC cells and caecal biopsies alongside bacterial motility and biofilm formation. The sub-inhibitory concentration also considerably reduced LDH release from infected PECC cells. It drastically attenuated the inflammatory response, as measured by levels of interferons (IFN) and cytokines IL-1β, IL-6, and IL-8 in infected PECC cells and in chicken caecal biopsies. These results were also mirrored when caecal biopsies were infected. The presence of As during infection also significantly reduced intracellular Ca2+ levels in both PECC cells and caecal biopsies and restored TEER levels. Conclusively, As reduces bacterial invasion in PECC cells and caecal biopsies, impairs bacterial growth, and causes bacterial membrane permeabilisation. It further reduces cytotoxicity and inflammation in PECC cells and caecal biopsies, apparently through a mechanism that involves regulation of intracellular calcium levels.

Keywords:  PECC cells; S. Typhimurium; caecal biopsies; calcium metabolism; membrane integrity; organic acids

DOI:  https://doi.org/10.1016/j.micpath.2026.108406
Antioxid Redox Signal. 2026 Feb 27. 15230864261425887

Dysregulated Copper Metabolism-Induced Cuproptosis Contributes to Mitochondrial Dysfunction and Macrophage Inflammatory Response in Acute Lung Injury.

Shuyang Chen, Zheng Zhou, Yajun Wang, Dong Yang, Jinjun Jiang, Shujing Chen.

   AIMS: To determine whether dysregulated copper metabolism and cuproptosis contribute to acute lung injury (ALI), and to evaluate whether targeting copper homeostasis mitigates lung inflammation and injury.
RESULTS: Integrative analysis of RNA-seq data from patients with severe community-acquired pneumonia revealed increased enrichment of copper metabolism-related gene sets and differential expression of cuproptosis-related genes. Notably, immune deconvolution of patient RNA-seq data demonstrated prominent macrophage enrichment, suggesting that macrophages represent a major cell group in which dysregulated copper metabolism may occur during ALI. In a lipopolysaccharide (LPS)-induced mouse ALI model, lung copper levels were elevated, accompanied by molecular features of cuproptosis, including increased DLAT oligomerization and destabilization of Fe-S cluster proteins. Pretreatment with the copper chelator tetrathiomolybdate alleviated lung injury and inflammatory response, while suppressing cuproptosis-related molecular features in vivo. In alveolar macrophages, LPS challenge increased intracellular Cu+ concentration and promoted DLAT oligomerization, and impaired Fe-S protein stability. Mechanistically, both copper chelation and knockdown of upstream cuproptosis regulator reduced DLAT oligomerization, restored Fe-S proteins, alleviated mitochondrial dysfunction, and decreased CD86+ macrophage polarization. Importantly, altered expression of copper transporters was observed, suggesting a remodeling of copper metabolic homeostasis during ALI.
INNOVATION AND CONCLUSION: This study identifies cuproptosis as a previously unrecognized driver of ALI, mechanistically linking copper dysregulation to mitochondrial damage and inflammatory activation of alveolar macrophages, and demonstrates the therapeutic benefit of copper chelation or cuproptosis suppression. Antioxid. Redox Signal. 00, 000-000.

Keywords:  acute lung injury; alveolar macrophages; copper metabolism; cuproptosis; mitochondrial dysfunction; oxidative stress

DOI:  https://doi.org/10.1177/15230864261425887