Activation of T-cells and Activity of Macrophages among Smokers with Leptospirosis: a Synergistic Dynamics in the Impairment of Human Immune System

Sumalapao, Derick Erl Perida; Lao, Angelyn Relucio; Adriano, Athena Acain; So, Jenny Carmina Gan; Gloriani, Nina Gonzales

doi:10.1590/1678-4324-2023220183

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Article - Human and Animal Health • Braz. arch. biol. technol. 66 • 2023 • https://doi.org/10.1590/1678-4324-2023220183 copy

Activation of T-cells and Activity of Macrophages among Smokers with Leptospirosis: a Synergistic Dynamics in the Impairment of Human Immune System

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Continuous heavy rains along with poor road construction and sewage system had resulted in the frequent occurrence of floods in many areas of the Philippines. As a consequence, leptospirosis remains an infectious disease endemic in the Philippines with numerous cases reported as aftermaths of typhoons especially after heavy flooding. Leptospirosis is known for its invasiveness in penetrating mucous membranes and abraded skin, in inducing macrophage response activity, and in activating T-cell proliferation. Chronic exposure to tobacco smoking weakens the immune system by reducing macrophage phagocytic activity and conferring T-cell insensitivity. In this study, a system of ordinary differential equations was developed to describe the synergy of leptospirosis and smoking in the impairment of immune system. The rate capacities of macrophages and T-cells in response to both smoking and leptospirosis were calculated. In the disease-free model, population of macrophages remains larger when compared with T-cells, and this predominance persists in the synergistic immune response to both smoking and leptospirosis. Leptospira infection in human immune cells is dose-dependent, and is more rapid in smoking-impaired than the normal cells. Findings of the study on these parameter estimates characterize the functions of macrophage and T-cell populations, although further molecular studies are warranted, which are necessary to address the inadequacy of antibiotic therapy in advanced and severe leptospirosis cases.

Keywords:
leptospirosis; macrophages; immune system; ordinary differential equations; tobacco smoking

HIGHLIGHTS

• Rate capacities of immune cell responses were computed using ordinary differential equations.

• Macrophages were predominant in the synergistic immune response to smoking and leptospirosis.

• Leptospira infection in human immune cells is dose-dependent.

• Leptospira infection is more rapid in smoking-impaired than the normal cells.

Parameter	Description	Value	Reference	Units
$r$	T-cells recruitment constant	0.3288	[¹⁹19 Das P, Mukherjee D, Sen A, Mukandavire Z, Chiyaka C. Analysis of an in-host model for HIV dynamics with saturation effect and discrete time delay. Nonlinear Dynamics and Systems Theory. 2011;11(2):125-36.]	day⁻¹
$k$	Macrophages recruitment rate	0.0876	[²²22 Adams BM, Banks HT, Davidian M, Kwon H, Tran H, Wynne S, et al. HIV dynamics: Modeling, data analysis, and optimal treatment protocols. J Comput Appl Math. 2005;184(1):10-49.]	cell . day⁻¹ . ml⁻¹
$γ_{T}$	T-cells natural mortality rate	5.48 ×10⁻⁵	[²⁰20 Wang X, Song X. Global stability and periodic solution of a model for HIV infection of CD4+ T cells. Appl Math Comput. 2007;189(2):1331-40.]	day⁻¹
$γ_{M}$	Macrophages natural mortality rate	9.62 ×10⁻⁶	[²¹21 Irunde JI, Luboobi LS, Nkansah-Gyekye Y. Modeling the effect of tobacco smoking on the in-host dynamics of HIV/AIDS. J Math Comput Sci. 2016;6(3):406-36.]	day⁻¹
$γ_{L}$	Leptospire natural mortality rate	5.5 x 10⁻³	[³¹31 Cox S. Leptospirosis a bacterial disease that's spreading. 2013 [cited 2018 August 30]. Available from: https://www.thewildest.com/dog-health/leptospirosis. https://www.thewildest.com/dog-health/le... ]	day⁻¹
$ε$	Macrophage smoking impairment rate	1.096 ×10⁻⁵	[²¹21 Irunde JI, Luboobi LS, Nkansah-Gyekye Y. Modeling the effect of tobacco smoking on the in-host dynamics of HIV/AIDS. J Math Comput Sci. 2016;6(3):406-36.]	day⁻¹
$δ$	T-cells smoking impairment rate	6.85 ×10⁻⁶	[²¹21 Irunde JI, Luboobi LS, Nkansah-Gyekye Y. Modeling the effect of tobacco smoking on the in-host dynamics of HIV/AIDS. J Math Comput Sci. 2016;6(3):406-36.]	day⁻¹
$γ_{T S}$	Impaired T-cells mortality rate	6.58 ×10⁻⁷	[²¹21 Irunde JI, Luboobi LS, Nkansah-Gyekye Y. Modeling the effect of tobacco smoking on the in-host dynamics of HIV/AIDS. J Math Comput Sci. 2016;6(3):406-36.]	day⁻¹
$γ_{M S}$	Impaired macrophages mortality rate	4.11 ×10⁻⁵	[²¹21 Irunde JI, Luboobi LS, Nkansah-Gyekye Y. Modeling the effect of tobacco smoking on the in-host dynamics of HIV/AIDS. J Math Comput Sci. 2016;6(3):406-36.]	day⁻¹
$γ_{T L}$	Infected T-cells mortality rate	1 ×10⁻⁴	Estimated	day⁻¹
$γ_{M L}$	Infected macrophages mortality rate	4 ×10⁻⁴	Estimated	day⁻¹
$μ$	Infected macrophages infection rate of normal T-cells	8 ×10⁻⁵	Estimated	day⁻¹
$μ_{T}$	Leptospire replication rate in infected T-cells	0.06	Estimated	day⁻¹
$μ_{M}$	Leptospire replication rate in infected macrophages	0.03	Estimated	day⁻¹
$α_{1}$	Infection rate for normal T-cells	5 ×10⁻⁵	Estimated	day⁻¹
$α_{2}$	Infection rate for impaired T-cells	3 ×10⁻⁴	Estimated	day⁻¹
$α_{3}$	Infection rate for normal macrophages	1 ×10⁻⁴	Estimated	day⁻¹
$α_{4}$	Infection rate for impaired macrophages	5 ×10⁻⁴	Estimated	day⁻¹

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[1] *Correspondence: dpsumalapao1@up.edu.ph; Tel.: +6325247118 (D.S.)