Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2024.10.10.617696

Obesity-Associated Changes in Immune Cell Dynamics During Alphavirus Infection Revealed by Single Cell Transcriptomic Analysis

Hameed, M.·Daamen, A.·Hossain, M. S.·Coutermarsh-Ott, S.·Lipsky, P. E.·Weger-Lucarelli, J.
View original source ↗Export metadata ↓

Abstract

Obesity induces diverse changes in host immunity, resulting in worse disease outcomes following infection with various pathogens, including arthritogenic alphaviruses. However, the impact of obesity on the functional landscape of immune cells during arthritogenic alphavirus infection remains unexplored. Here, we used single-cell RNA sequencing (scRNA-seq) to dissect the blood and tissue immune responses to Mayaro virus (MAYV) infection in lean and obese mice. Footpad injection of MAYV caused significant shifts in immune cell populations and induced robust expression of interferon response and proinflammatory cytokine genes and related pathways in both blood and tissue. In MAYV-infected lean mice, analysis of the local tissue response revealed a unique macrophage subset with high expression of IFN response genes that was not found in obese mice. This was associated with less severe inflammation in lean mice. These results provide evidence for a unique macrophage population that may contribute to the superior capacity of lean mice to control arthritogenic alphavirus infection. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/617696v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@11e9cbdorg.highwire.dtl.DTLVardef@c44512org.highwire.dtl.DTLVardef@192da94org.highwire.dtl.DTLVardef@4c5ea5_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIObesity worsens disease outcomes following arthritogenic alphavirus infection. C_LIO_LIArthritogenic alphavirus infection causes significant shifts in immune cell populations in the blood and footpad. C_LIO_LIBlood monocytes from lean mice had higher expression of interferon response genes at the later stage of infection. C_LIO_LIFootpads in lean mice have an expanded population of F4/80lo macrophages with an intense interferon response gene signature before and after alphavirus infection that is not found in obese mice. C_LIO_LIMacrophages in obese mice express lower levels of interferon response genes, have a unique necroptosis signature, and higher F4/80 expression. C_LI

Explore related subjects

immunologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Hameed, M., Daamen, A., Hossain, M. S., Coutermarsh-Ott, S., Lipsky, P. E., Weger-Lucarelli, J.. 2024-10-13. Obesity-Associated Changes in Immune Cell Dynamics During Alphavirus Infection Revealed by Single Cell Transcriptomic Analysis. https://doi.org/10.1101/2024.10.10.617696

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Dynamic Responses to an Inflammatory Challenge Distinguish Metabolic Health Across Lean and Obese Individuals

Inflammation is a key driver of cardiometabolic disease, yet it remains unclear whether systemic inflammatory markers can distinguish metabolically healthy from unhealthy individuals or capture the temporal dynamics of inflammation. Here, we combined systemic immune profiling with a cantharidin-induced peripheral blister model to investigate dynamic inflammatory regulation across metabolic phenotypes in metabolically healthy lean (MHL), metabolically unhealthy lean (MUL), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) individuals. While systemic inflammation was elevated in obesity, differences between metabolically healthy and unhealthy groups were modest, with limited discrimination by plasma proteomics, circulating leukocyte phenotyping, and whole-blood transcriptomics. In contrast, the dynamic response to inflammatory challenge revealed pronounced differences at proteomic, cellular, and transcriptomic levels. Metabolically unhealthy individuals exhibited exaggerated early innate immune responses, impaired inflammatory resolution and tissue repair, reduced recruitment of reparative immune cells, and sustained T cell presence. Transcriptomic analyses further showed blunted dynamic gene regulation and defective epidermal barrier restoration. These findings indicate that metabolic health is better reflected in tissue-level inflammatory dynamics than in systemic measures.

immunology↗
bioRxiv2026

Risk factors and immunological characteristics of SARS-CoV-2 RNA re-positivity in convalescent COVID-19 Patients: A retrospective study

Purpose: To investigate the incidence, clinical features, and risk factors for SARS-CoV-2 nucleic acid re-positivity in recovered COVID-19 patients. Methods: We enrolled 441 convalescent COVID-19 patients from the rehabilitation ward of the Fifth Hospital of Shijiazhuang between January and April 2021. Based on nucleic acid test results, patients were categorized into repositive (n = 69) and non-repositive (n = 372) groups. Demographic, clinical, laboratory, and imaging data were compared between groups. Logistic regression was used to identify factors associated with re-positivity. Results: The overall re-positivity rate was 15.65%. Compared with the non-repositive group, the repositive group presented with a significantly higher proportion of moderate disease severity (72.46% vs. 50.54%) and a lower proportion of patients under 14 years old (7.25% vs. 23.66%). Additionally, multi-lobar involvement ([&ge;] 3 lobes) during the acute phase was more common in the repositive group (43.48% vs. 26.61%), with all differences being statistically significant (P < 0.001). Laboratory analysis revealed that repositive patients had significantly lower lymphocyte and eosinophil counts, as well as reduced albumin (ALB), aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, and albumin/globulin (A/G) ratio. Furthermore, circulating CD3+, CD4+, and CD8+ T-cell counts were markedly decreased. In contrast, the neutrophil-to-lymphocyte ratio (NLR), immunoglobulin M (IgM), immunoglobulin A (IgA), and neutralizing antibody (NAb) levels were significantly elevated in re-positive patients (all P < 0.05). Multivariate logistic regression analysis identified the CD8+ as independent risk factors for re-positivity. Conclusion: In convalescent patients, SARS-CoV-2 RNA re-positivity correlates with distinct clinical and immunological characteristics. The CD8+ T-cell level is an independent predictor, highlighting that dysregulated immune and inflammatory responses contribute to delayed viral clearance.

immunology↗
bioRxiv2026

Efficacy of rDiHAVO as a potential vaccine antigen against heartworm infections in a mouse model

Dirofilariasis, or heartworm disease, is a life-threatening parasitic infection caused by the nematode parasite Dirofilaria immitis. Mosquito vectors in tropical and subtropical regions transmit the infection. Current treatment options are expensive, have a short-term effect, and depend on anthelminthic therapy. There are no licensed vaccines available for preventing heartworm infections. The primary goal of this study was to identify potential vaccine candidates, develop a tetravalent fusion protein (rDiHAVO) vaccine antigen, and evaluate its immunogenicity and efficacy in a mouse model of D. immitis infection. Results show that the rDiHAVO is highly immunogenic in mice and confers over 95% protection against a challenge infection. These findings suggest that rDiHAVO is a potential vaccine candidate against Dirofilariasis. Additional testing in dogs can advance this vaccine candidate to clinical trials.

immunology↗