Sex-specific responses of monocytes to infectious challenges

Monocytes play an important role in immune control of infections and in the success of vaccination. Like other cells of the immune system, monocytes are influenced by biological, sex-specific factors. For example, many parasitic diseases such as leishmaniasis and amebiasis occur more frequently in males. The mouse model for hepatic amebiasis mimics the sex difference as observed in humans and substitution of females with testosterone abolished their resistance. As key mediators of inflammation, monocytes must be tightly regulated, but when this is not the case, as in amebiasis, excessive activation can result in immunopathology and destruction of host tissue. Our previous investigations revealed that TNFα and recruitment of classical, inflammatory monocytes and neutrophils substantially contribute to liver damage during parasitic infection. The underlying immune cascade involves the IL-23/IL-17 immune axis and monocyte/neutrophil-attracting cytokines like chemokine ligand (CCL) 2 and the C-X-C motif ligand 1 (CXCL1). Intriguingly, TNFα and both chemokines are higher in male compared to female mice and partially also in humans upon infectious challenge. The production of these proinflammatory cytokines is further increased by treatment with the most active androgen, dihydrotestosterone. On the other hand, the prerequisites to recognize a foreign antigen are stronger in monocytes of female individuals. This also leads, for example, to a stronger vaccination response in women than in men. Among other mechanisms, certain Fcgamma receptors on the surface of monocytes are responsible for this.

We hypothesize that sex hormones substantially modulate monocyte functions and aim to investigate essentially underlying androgen-dependent signaling pathways

The immune response to foreign agents differs between women and men.
We will study the influence of sex hormones on cells of the innate immune system and the impact on the efficacy of vaccination and the outcome of parasitic infection.

Groneberg M, Hoenow S, Marggraff C, Fehling H, Metwally NG, Hansen C, Bruchhaus I, Tiegs G, Sellau J, Lotter H. (2021)
HIF-1α modulates sex-specific Th17/Treg responses during hepatic amoebiasis
J Hepatol. S0168-8278(21)02082-1. Online ahead of print.

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Sellau J, Groneberg M, Hoenow S, Lotter H. (2021)
The underlying cellular immune pathology of Entamoeba histolytica-induced hepatic amoebiasis
J Hepatol 75:481-482

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Tuku B, Stanelle -Bertram S, Sellau J, Beck S, Bai T, Mounogue Kouassi N, Preuß A, Hoenow S, Renné T, Lotter H, Gabriel G. (2020)
Testosterone protects against severe influenza by reducing the pro-inflammatory cytokine response in the murine lung
Front Immunol 11:697

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Sellau J, Groneberg M, Lotter H. (2019)
Androgen-dependent immune modulation in parasitic infections
Sem Immunopathol 41:213-224

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Stanelle-Bertram S, .... Sellau J, .....Arck P.... Friese, MA .... Lotter H .... Gabriel G. (2018)
Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood
Nat Microbiol 3:1161-1174

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Noll J, Fehling H, Bernin H, Marggraff C, Jacobs T, Huber S, Pelczar P, Ernst T, Ittrich H, Otto B, Mittrucker H W, Hoelscher C, Tacke F, Bruchhaus I, Tannich E, Lotter, H. (2016)
IL-23 prevents IL-13-dependent tissue repair associated with Ly6C(lo) monocytes in Entamoeba histolytica-induced liver damage
J Hepatol 64:1147-1157

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Helk E, Bernin H, Ernst T, Ittrich H, Jacobs T, Heeren J, Tacke F, Tannich E, Lotter H. (2013)
TNFalpha-mediated liver destruction by Kupffer cells and Ly6Chi and Ly6Chi monocytes during Entamoeba histolytica infection
PLoS Pathog 9:e1003096

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