Latest Publications



Johnson BL 3rd, Midura EF, Prakash PS, Rice TC, Kunz N, Kalies K, Caldwell CC. Neutrophil derived microparticles increase mortality and the counter-inflammatoryresponse in a murine model of sepsis. Biochim Biophys Acta. 2017 Jan 17. pii:S0925-4439(17)30017-0. doi: 10.1016/j.bbadis.2017.01.012. [Epub ahead of print] PubMed PMID: 28108420.

Although advances in medical care have significantly improved sepsis survival, sepsis remains the leading cause of death in the ICU. This is likely due to a lack of complete understanding of the pathophysiologic mechanisms that lead to dysfunctional immunity. Neutrophil derived microparticles (NDMPs) have been shown to be the predominant microparticle present at infectious and inflamed foci in human models, however their effect on the immune response to inflammation and infection is sepsis has not been fully elucidated. As NDMPs may be a potential diagnostic and therapeutic target, we sought to determine the impact NDMPs on the immune response to a murine polymicrobial sepsis. We found that peritoneal neutrophil numbers, bacterial loads, and NDMPs were increased in our abdominal sepsis model. When NDMPs were injected into septic mice, we observed increased bacterial load, decreased neutrophil recruitment, increased expression of IL-10 and worsened mortality. Furthermore, the NDMPs express phosphatidylserine and are ingested by F4/80 macrophages via a Tim-4 and MFG-E8 dependent mechanism. Finally, upon treatment, NDMPs decrease macrophage activation, increase IL-10 release and decrease macrophage numbers. Altogether, these data suggest that NDMPs enhance immune dysfunction in sepsis by blunting the function of neutrophils and macrophages, two key cell populations involved in the early immune response to infection. This article is part of a Special Issue entitled: Immune and Metabolic Alterations in Trauma and Sepsis - edited by Raghavan Raju.



Milićević NM, Schmidt F, Kunz N, Kalies K, Milićević Ž, Schlosser A, Holmskov U, Sorensen GL, Westermann J. The role of microfibrillar-associated protein 4(MFAP4) in the formation and function of splenic compartments during embryonicand adult life. Cell Tissue Res. 2016 Jul;365(1):135-45.  PubMed PMID: 26899386

Pagel J, Hartz A, Figge J, Gille C, Eschweiler S, Petersen K, Schreiter L,Hammer J, Karsten CM, Friedrich D, Herting E, Göpel W, Rupp J, Härtel C.Regulatory T cell frequencies are increased in preterm infants with clinicalearly-onset sepsis. Clin Exp Immunol. 2016 Aug;185(2):219-27. PubMed PMID: 27163159

Hoffmann F, Ender F, Schmudde I, Lewkowich IP, Köhl J, König P, Laumonnier Y. Origin, Localization, and Immunoregulatory Properties of Pulmonary Phagocytes in Allergic Asthma. Front Immunol. 2016 Mar 23;7:107. Review. PubMed PMID: 27047494.

Midura EF, Prakash PS, Johnson BL 3rd, Rice TC, Kunz N, Caldwell CC. Impact ofcaspase-8 and PKA in regulating neutrophil-derived microparticle generation. Biochem Biophys Res Commun. 2016 Jan 22;469(4):917-22. PubMed PMID: 26707875.




Köhl J, Moreno-Fernandez ME, Aliberti J, Groeneweg S, Chougnet C. A novel rolefor the receptor of the complement cleavage fragment C5a, C5aR1, in CCR5-mediatedentry of HIV into macrophages. AIDS Res Hum Retroviruses. 2015 Nov 5. PubMed PMID: 26537334.

Bollinger T, Bollinger A, Gies S, Feldhoff L, Solbach W, Rupp J. Transcriptionregulates HIF-1α expression in CD4(+) T cells. Immunol Cell Biol. 2015 Jul 7. PubMed PMID: 26150319.

Karsten CM, Laumonnier Y, Eurich B, Ender F, Bröker K, Roy S, Czabanska A,
Vollbrandt T, Figge J, Köhl J. Monitoring and Cell-Specific Deletion of C5aR1
Using a Novel Floxed GFP-C5aR1 Reporter Knock-in Mouse. J Immunol. 2015 Jan 14. pii: 1401401.PubMed PMID: 25589074




Strait RT, Posgai MT, Mahler A, Barasa N, Jacob CO, Köhl J, Ehlers M, Stringer K, Shanmukappa SK, Witte D, Hossain MM, Khodoun M, Herr AB, Finkelman FD. IgG1protects against renal disease in a mouse model of cryoglobulinaemia. Nature.2014 Nov 2. PubMed PMID:25363774.


Engelke C, Wiese AV, Schmudde I, Ender F, Ströver HA, Vollbrandt T, König P,
Laumonnier Y, Köhl J
. Distinct roles of the anaphylatoxins C3a and C5a in
dendritic cell-mediated allergic asthma. J Immunol. 2014 Dec 1;193(11):5387-401. PubMed PMID: 25355927.


Bollinger T, Gies S, Naujoks J, Feldhoff L, Bollinger A, Solbach W, Rupp J.
HIF-1α- and hypoxia-dependent immune responses in human CD4+CD25high T cells and T helper 17 cells. J Leukoc Biol. 2014 Aug;96(2):305-12. PubMed PMID: 24664971


Berod L, Stüve P, Varela F, Behrends J, Swallow M, Kruse F, Krull F, Ghorbani P, Mayer CT, Hölscher C, Sparwasser T. Rapid rebound of the Treg compartment inDEREG mice limits the impact of Treg depletion on mycobacterial burden, butprevents autoimmunity. PLoS One. 2014 Jul 22;9(7):e102804.  PubMed PMID: 25050936.


Schmitz V, Almeida LN, Svensjö E, Monteiro AC, Köhl J, Scharfstein J. C5a and Bradykinin Receptor Cross-Talk Regulates Innate and Adaptive Immunity inTrypanosoma cruzi Infection. J Immunol. 2014 Oct 1;193(7):3613-23. Epub 2014 Sep 3. PubMed PMID: 25187655.





Hess C, Winkler A, Lorenz AK, Holecska V, Blanchard V, Eiglmeier S, Schoen AL, Bitterling J, Stoehr AD, Petzold D, Schommartz T, Mertes MM, Schoen CT, Tiburzy B, Herrmann A, Köhl J, Manz RA, Madaio MP, Berger M, Wardemann H, Ehlers M. T cell-independent B cell activation induces immunosuppressive sialylated IgG antibodies. J Clin Invest. 2013 Sep 3;123(9):3788-96. PMID:23979161


Kemper C, Köhl J. Novel roles for complement receptors in T cell regulation and beyond. Mol Immunol. 2013 Jun 21. PubMed PMID: 23796748.


Schmudde I, Laumonnier Y, Köhl J. Anaphylatoxins coordinate innate and adaptive immune responses in allergic asthma. Semin Immunol. 2013 May 19. PubMed PMID: 23694705.